Publications
| Title | Abstract | Year(sorted descending) Filter | PMID Filter |
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| grammomys surdaster, the natural host for plasmodium berghei parasites, as a model to study whole-organism vaccines against malaria. | inbred mice are commonly used to test candidate malaria vaccines, but have been unreliable for predicting efficacy in humans. to establish a more rigorous animal model, we acquired african woodland thicket rats of the genus grammomys, the natural hosts for plasmodium berghei thicket rats were acquired and identified as grammomys surdaster by skull and teeth measurements and mitochondrial dna genotyping. herein, we demonstrate that thicket rats are highly susceptible to infection by p berghei, an ... | 2017 | 28115674 |
| crispr/cas9 mediated sequential editing of genes critical for ookinete motility in plasmodium yoelii. | crispr/cas9 has been successfully adapted for gene editing in malaria parasites including plasmodium falciparum and plasmodium yoelii. however, the reported methods were limited to editing one gene at a time. in practice, it is often desired to modify multiple genetic loci in a parasite genome. here we describe a crispr/cas9 mediated genome editing method that allows successive modification of more than one gene in the genome of p. yoelii using an improved single-vector system (pycm) we develope ... | 2017 | 28034675 |
| antimalarial activity of novel 4-aminoquinolines active against drug resistant strains. | in the present study we have synthesized a new class of 4-aminoquinolines and evaluated against plasmodium falciparum in vitro (3d7-sensitive strain & k1-resistant strain) and plasmodium yoelii in vivo (n-67 strain). among the series, eleven compounds (5, 6, 7, 8, 9, 11, 12, 13, 14, 15 and 21) showed superior antimalarial activity against k1 strain as compared to cq. in addition, all these analogues showed 100% suppression of parasitemia on day 4 in the in vivo mouse model against n-67 strain wh ... | 2017 | 27908538 |
| mir-451 limits cd4(+) t cell proliferative responses to infection in mice. | micrornas (mirnas) are major regulators of cell responses, particularly in stressed cell states and host immune responses. some mirnas have a role in pathogen defense, including regulation of immune responses to plasmodium parasite infection. using a nonlethal mouse model of blood stage malaria infection, we have found that mir-451(-/-) mice infected with plasmodium yoelii xnl cleared infection at a faster rate than did wild-type (wt) mice. mir-451(-/-) mice had an increased leukocyte response t ... | 2017 | 28378118 |
| magnetic nanovectors for the development of dna blood-stage malaria vaccines. | dna vaccines offer cost, flexibility, and stability advantages, but administered alone have limited immunogenicity. previously, we identified optimal configurations of magnetic vectors comprising superparamagnetic iron oxide nanoparticles (spions), polyethylenimine (pei), and hyaluronic acid (ha) to deliver malaria dna encoding plasmodium yoelii (py) merozoite surface protein msp119 (spions/pei/dna + ha gene complex) to dendritic cells and transfect them with high efficiency in vitro. herein, we ... | 2017 | 28336871 |
| dc-derived il-10 modulates pro-inflammatory cytokine production and promotes induction of cd4(+)il-10(+) regulatory t cells during plasmodium yoelii infection. | the cytokine il-10 plays a crucial role during malaria infection by counteracting the pro-inflammatory immune response. we and others demonstrated that plasmodium yoelii infection results in enhanced il-10 production in cd4(+) t cells accompanied by the induction of an immunosuppressive phenotype. however, it is unclear whether this is a direct effect caused by the parasite or an indirect consequence due to t cell activation by il-10-producing antigen-presenting cells. here, we demonstrate that ... | 2017 | 28293237 |
| myeloperoxidase attenuates pathogen clearance during plasmodium yoelii nonlethal infection. | myeloperoxidase (mpo), a leukocyte-derived enzyme mainly secreted by activated neutrophils, is known to be involved in the immune response during bacterial and fungal infection and inflammatory diseases. nevertheless, the role of mpo in a parasitic disease like malaria is unknown. we hypothesized that mpo contributes to parasite clearance. to address this hypothesis, we used plasmodium yoelii nonlethal infection in wild-type and mpo-deficient mice as a murine malaria model. we detected high mpo ... | 2017 | 27795354 |
| differential spleen remodeling associated with different levels of parasite virulence controls disease outcome in malaria parasite infections. | infections by malaria parasites can lead to very different clinical outcomes, ranging from mild symptoms to death. differences in the ability of the spleen to deal with the infected red blood cells (irbcs) are linked to differences in virulence. using virulent and avirulent strains of the rodent malaria parasite plasmodium yoelii, we investigated how parasite virulence modulates overall spleen function. following parasite invasion, a difference in parasite virulence was observed in association w ... | 2017 | 27303680 |
| resistance and susceptibility to malarial infection: a host defense strategy against malaria. | in an effort to understand what limits the virulence of malaria parasites in relation to the host genetic and immunogenic background, we investigated the possibility that the parasite and host genotype crossover interactions constrain virulence. | 2017 | 26811732 |
| adaptive immunity is essential in preventing recrudescence of plasmodium yoelii malaria parasites after artesunate treatment. | artemisinin-based antimalarials, such as artesunate (art), alone or in combination, are the mainstay of the therapy against malaria caused by plasmodium falciparum. however, the emergence and spread of artemisinin resistance threatens the future success of its global malaria eradication. although much of the reported artemisinin resistance can be attributed to mutations intrinsic to the parasite, a significant proportion of treatment failures are thought to be due to other factors such as the ho ... | 2017 | 28664674 |
| host-mediated impairment of parasite maturation during blood-stage plasmodium infection. | severe malaria and associated high parasite burdens occur more frequently in humans lacking robust adaptive immunity to plasmodium falciparum nevertheless, the host may partly control blood-stage parasite numbers while adaptive immunity is gradually established. parasite control has typically been attributed to enhanced removal of parasites by the host, although in vivo quantification of this phenomenon remains challenging. we used a unique in vivo approach to determine the fate of a single coho ... | 2017 | 28673996 |
| abscisic acid induces a transient shift in signaling that enhances nf-κb-mediated parasite killing in the midgut of anopheles stephensi without reducing lifespan or fecundity. | abscisic acid (aba) is naturally present in mammalian blood and circulating levels can be increased by oral supplementation. we showed previously that oral aba supplementation in a mouse model of plasmodium yoelii 17xnl infection reduced parasitemia and gametocytemia, spleen and liver pathology, and parasite transmission to the mosquito anopheles stephensi fed on these mice. treatment of cultured plasmodium falciparum with aba at levels detected in our model had no effects on asexual growth or g ... | 2017 | 28705245 |
| immunization with the malaria diversity-covering blood-stage vaccine candidate plasmodium falciparum apical membrane antigen 1 dico in complex with its natural ligand pfron2 does not improve the in vitro efficacy. | the blood-stage malaria vaccine candidate plasmodium falciparum apical membrane antigen 1 (pfama1) can induce strong parasite growth-inhibitory antibody responses in animals but has not achieved the anticipated efficacy in clinical trials. possible explanations in humans are the insufficient potency of the elicited antibody responses, as well as the high degree of sequence polymorphisms found in the field. several strategies have been developed to improve the cross-strain coverage of pfama1-base ... | 2017 | 28702028 |
| development of loop-mediated isothermal amplification with plasmodium falciparum unique genes for molecular diagnosis of human malaria. | in order to achieve better outcomes for treatment and in the prophylaxis of malaria, it is imperative to develop a sensitive, specific, and accurate assay for early diagnosis of plasmodium falciparum infection, which is the major cause of malaria. in this study, we aimed to develop a loop-mediated isothermal amplification (lamp) assay with p. falciparum unique genes for sensitive, specific, and accurate detection of p. falciparum infection. the unique genes of p. falciparum were randomly selecte ... | 2017 | 28683669 |
| investigation of the component in artemisia annua l. leading to enhanced antiplasmodial potency of artemisinin via regulation of its metabolism. | the chemical matrix of the herb artemisia annua l. (a. annua), from which artemisinin (qhs) is isolated, can enhance both the bioavailability and efficacy of qhs. however, the exact mechanism of this synergism remains unknown. the biotransformation of qhs and potential "enzyme inhibitors" in plant matrix could be of great importance in understanding the improved efficacy of qhs in a. annua, which has been limited to the synergism with flavonoid components. | 2017 | 28642094 |
| correlation between in vitro and in vivo antimalarial activity of compounds using cq-sensitive and cq-resistant strains of plasmodium falciparum and cq-resistant strain of p. yoelii. | present efforts have been made to establish a correlation between in vitro and in vivo antimalarial activity using mic, ic50 and ic90 values against cq-sensitive (3d7) and cq-resistant (k1) strains of plasmodium falciparum and in vivo activity against plasmodium yoelii. the method of discriminant function analysis (dfa) was applied to analyze the data. it was observed that in vitro ic90 values against both 3d7 and k1 strains (p < 0.001) have strong correlation with in vivo curative activity. the ... | 2017 | 28502016 |
| differential gene expression in anopheles stephensi following infection with drug-resistant plasmodium yoelii. | the transmission of drug-resistant parasites by the mosquito may be influenced by the altered biological fitness of drug-resistant parasites and different immune reactions or metabolic change in the mosquito. at this point, little is known about the variations in mosquito immunity and metabolism when mosquitoes are infected with drug-resistant parasites. to understand the differential gene expression in anopheles following infection with drug-resistant plasmodium, we conducted a genome-wide tran ... | 2017 | 28851458 |
| a plasmodium yoelii hect-like e3 ubiquitin ligase regulates parasite growth and virulence. | infection of mice with strains of plasmodium yoelii parasites can result in different pathology, but molecular mechanisms to explain this variation are unclear. here we show that a p. yoelii gene encoding a hect-like e3 ubiquitin ligase (pyheul) influences parasitemia and host mortality. we genetically cross two lethal parasites with distinct disease phenotypes, and identify 43 genetically diverse progeny by typing with microsatellites and 9230 single-nucleotide polymorphisms. a genome-wide quan ... | 2017 | 28790316 |
| alba4 modulates its stage-specific interactions and specific mrna fates during plasmodium yoelii growth and transmission. | transmission of the malaria parasite occurs in an unpredictable moment, when a mosquito takes a blood meal. plasmodium has therefore evolved strategies to prepare for transmission, including translationally repressing and protecting mrnas needed to establish the infection. however, mechanisms underlying these critical controls are not well understood, including whether plasmodium changes its translationally repressive complexes and mrna targets in different stages. efforts to understand this hav ... | 2017 | 28787542 |
| il-17 promotes differentiation of splenic lsk(-) lymphoid progenitors into b cells following plasmodium yoelii infection. | lineage(-)sca-1(+)c-kit(-) (lsk(-)) cells are a lymphoid progenitor population that expands in the spleen and preferentially differentiates into mature b cells in response to plasmodium yoelii infection in mice. furthermore, lsk(-) derived b cells can subsequently contribute to the ongoing immune response through the generation of parasite-specific ab-secreting cells, as well as germinal center and memory b cells. however, the factors that promote their differentiation into b cells in the spleen ... | 2017 | 28733485 |
| isolation and characterization of vaccine candidate genes including csp and msp1 in plasmodium yoelii. | malaria is an infectious disease affecting humans, which is transmitted by the bite of anopheles mosquitoes harboring sporozoites of parasitic protozoans belonging to the genus plasmodium. despite past achievements to control the protozoan disease, malaria still remains a significant health threat up to now. in this study, we cloned and characterized the full-unit plasmodium yoelii genes encoding merozoite surface protein 1 (msp1), circumsporozoite protein (csp), and duffy-binding protein (dbp), ... | 2017 | 28719950 |
| rapid identification of genes controlling virulence and immunity in malaria parasites. | identifying the genetic determinants of phenotypes that impact disease severity is of fundamental importance for the design of new interventions against malaria. here we present a rapid genome-wide approach capable of identifying multiple genetic drivers of medically relevant phenotypes within malaria parasites via a single experiment at single gene or allele resolution. in a proof of principle study, we found that a previously undescribed single nucleotide polymorphism in the binding domain of ... | 2017 | 28704525 |
| new gorilla adenovirus vaccine vectors induce potent immune responses and protection in a mouse malaria model. | a dna-human ad5 (huad5) prime-boost malaria vaccine has been shown to protect volunteers against a controlled human malaria infection. the potency of this vaccine, however, appeared to be affected by the presence of pre-existing immunity against the huad5 vector. since huad5 seroprevalence is very high in malaria-endemic areas of the world, huad5 may not be the most appropriate malaria vaccine vector. this report describes the evaluation of the seroprevalence, immunogenicity and efficacy of thre ... | 2017 | 28673287 |
| the transcription factor nfat1 participates in the induction of cd4(+) t cell functional exhaustion during plasmodium yoelii infection. | repeated stimulation of t cells that occurs in the context of chronic infection results in progressively reduced responsiveness of t cells to pathogen-derived antigens. this phenotype, known as t cell exhaustion, occurs during chronic infections caused by a variety of pathogens, from persistent viruses to parasites. unlike the memory cells that typically form after successful pathogen clearance following an acute infection, exhausted t cells secrete lower levels of effector cytokines, proliferat ... | 2017 | 28630062 |
| within-host selection of drug resistance in a mouse model of repeated interrupted treatment of plasmodium yoelii infection. | to study within-host selection of resistant parasites, an important factor in the development of resistance to anti-malarial drugs, a mouse model of repeated interrupted malaria treatment (rit) has been developed. the characteristics of within host selection of resistance to atovaquone and pyrimethamine in plasmodium yoelii was examined in such a model. | 2017 | 28535797 |
| a prime-boost immunization regimen based on a simian adenovirus 36 vectored multi-stage malaria vaccine induces protective immunity in mice. | malaria remains a considerable burden on public health. in 2015, the who estimates there were 212 million malaria cases causing nearly 429,000 deaths globally. a highly effective malaria vaccine is needed to reduce the burden of this disease. we have developed an experimental vaccine candidate (pycmp) based on pre-erythrocytic (csp) and erythrocytic (msp1) stage antigens derived from the rodent malaria parasite p. yoelii. our protein-based vaccine construct induces protective antibodies and cd4( ... | 2017 | 28483199 |
| co-localization of a cd1d-binding glycolipid with an adenovirus-based malaria vaccine for a potent adjuvant effect. | a cd1d-binding, invariant (i) natural killer t (nkt)-cell stimulatory glycolipid, α-galactosylceramide (αgalcer), has been shown to act as an adjuvant. we previously identified a fluorinated phenyl ring-modified αgalcer analog, 7dw8-5, displaying a higher binding affinity for cd1d molecule and more potent adjuvant activity than αgalcer. in the present study, 7dw8-5 co-administered intramuscularly (i.m.) with a recombinant adenovirus expressing a plasmodium yoelii circumsporozoite protein (pycsp) ... | 2017 | 28483194 |
| cellular immune response to dna and vaccinia prime-boost immunization kills plasmodium yoelii-infected hepatocytes in vitro. | plasmid dna encoding plasmodium yoelii circumsporozoite protein (pycsp) followed by boosting with recombinant vaccinia virus containing the pycsp elicited significant protective immunity in mice that was primarily mediated by cd8+ t-cell responses directed to p. yoelii -infected hepatocytes. this study was to further explore protection using in vitro cultures of p. yoelii parasites in mouse hepatocytes. spleen cells from dna/vaccinia virus-immunized mice were co-cultured in vitro with mouse hepa ... | 2017 | 28475711 |
| plasmodium parasite as an effective hepatocellular carcinoma antigen glypican-3 delivery vector. | we have previously demonstrated that malaria parasite infection has an anti-tumor effect in a mouse model. this research aimed to investigate the possibility of using plasmodium parasite as a novel vaccine vector for hepatocellular carcinoma (hcc) immunotherapy. we constructed a plasmodium yoelii 17xnl strain (p.y) expressing murine glypican-3 (gpc3) protein (p.y-gpc3), and examined its therapeutic potency in a murine hepa1-6-induced hepatoma model that highly expressed gpc3 protein. the prerequ ... | 2017 | 28445973 |
| cd36 receptor regulates malaria-induced immune responses primarily at early blood stage infection contributing to parasitemia control and resistance to mortality. | in malaria, cd36 plays several roles, including mediating parasite sequestration to host organs, phagocytic clearance of parasites, and regulation of immunity. although the functions of cd36 in parasite sequestration and phagocytosis have been clearly defined, less is known about its role in malaria immunity. here, to understand the function of cd36 in malaria immunity, we studied parasite growth, innate and adaptive immune responses, and host survival in wt and cd36(-/-) mice infected with a no ... | 2017 | 28416609 |
| genome-wide polymorphisms and development of a microarray platform to detect genetic variations in plasmodium yoelii. | the rodent malaria parasite plasmodium yoelii is an important model for studying malaria immunity and pathogenesis. one approach for studying malaria disease phenotypes is genetic mapping, which requires typing a large number of genetic markers from multiple parasite strains and/or progeny from genetic crosses. hundreds of microsatellite (ms) markers have been developed to genotype the p. yoelii genome; however, typing a large number of ms markers can be labor intensive, time consuming, and expe ... | 2016 | 24685548 |
| effect of anti-hyperlipidemia drugs on the alpha-tocopherol concentration and their potential for murine malaria infection. | the current preventions of malaria are protection against mosquito bites and taking chemoprophylactic anti-malarial drugs. however, drug therapies are usually associated with adverse events and emergency of drug-resistant malaria parasites. previous study showed that host plasma alpha-tocopherol deficiency enhanced resistance against malaria infection in mice. here, we report a new prevention strategy against malaria by using anti-hyperlipidemia drugs, ezetimibe, berberine, cholestyramine, and p ... | 2016 | 26358099 |
| plasmodium genetic loci linked to host cytokine and chemokine responses. | both host and parasite factors contribute to disease severity of malaria infection; however, the molecular mechanisms responsible for the disease and the host-parasite interactions involved remain largely unresolved. to investigate the effects of parasite factors on host immune responses and pathogenesis, we measured levels of plasma cytokines/chemokines (ccs) and growth rates in mice infected with two plasmodium yoelii strains having different virulence phenotypes and in progeny from a genetic ... | 2016 | 24452266 |
| utr introns, antisense rna and differentially spliced transcripts between plasmodium yoelii subspecies. | the rodent malaria parasite plasmodium yoelii is an important animal model for studying host-parasite interaction and molecular basis of malaria pathogenesis. although a draft genome of p. yoelii yoelii ym is available, and rna sequencing (rna-seq) data for several rodent malaria species (rmp) were reported recently, variations in coding regions and structure of mrna transcript are likely present between different parasite strains or subspecies. sequencing of cdna libraries from additional paras ... | 2016 | 26791272 |
| depletion of phagocytic cells during nonlethal plasmodium yoelii infection causes severe malaria characterized by acute renal failure in mice. | in the current study, we examined the effects of depletion of phagocytes on the progression of plasmodium yoelii 17xnl infection in mice. strikingly, the depletion of phagocytic cells, including macrophages, with clodronate in the acute phase of infection significantly reduced peripheral parasitemia but increased mortality. moribund mice displayed severe pathological damage, including coagulative necrosis in liver and thrombi in the glomeruli, fibrin deposition, and tubular necrosis in kidney. t ... | 2016 | 26755155 |
| chemically attenuated blood-stage plasmodium yoelii parasites induce long-lived and strain-transcending protection. | the development of a vaccine is essential for the elimination of malaria. however, despite many years of effort, a successful vaccine has not been achieved. most subunit vaccine candidates tested in clinical trials have provided limited efficacy, and thus attenuated whole-parasite vaccines are now receiving close scrutiny. here, we test chemically attenuated plasmodium yoelii 17x and demonstrate significant protection following homologous and heterologous blood-stage challenge. protection agains ... | 2016 | 27245410 |
| pymif enhances the inflammatory response in a rodent model by stimulating cd11b(+) ly6c(+) cells accumulation in spleen. | macrophage migration inhibitory factor (pmif) expressed by plasmodium parasites has been proved to be similar to the mammalian mif in both structure and biological activity and is a critical upstream regulator in antimalaria innate immunity. in this work, using a genetically modified (mif-ko) strain of highly lethal rodent plasmodium yoelii 17xl (py17xl), we found that pymif could increase the secretion of pro-inflammatory factors by eliciting the cd11b(+) ly6c(+) cells accumulated in the spleen ... | 2016 | 27028001 |
| plasmodium yoelii infection of balb/c mice results in expansion rather than induction of cd4(+) foxp3(+) regulatory t cells. | recently, we demonstrated elevated numbers of cd4(+) foxp3(+) regulatory t (treg) cells in plasmodium yoelii-infected mice contributing to the regulation of anti-malarial immune response. however, it remains unclear whether this increase in treg cells is due to thymus-derived treg cell expansion or induction of treg cells in the periphery. here, we show that the frequency of foxp3(+) treg cells expressing neuropilin-1 (nrp-1) decreased at early time-points during p. yoelii infection, whereas per ... | 2016 | 26932746 |
| repetitive live sporozoites inoculation under arteether chemoprophylaxis confers protection against subsequent sporozoite challenge in rodent malaria model. | inoculation with live sporozoites under prophylactic antimalarial cover (cps-immunization) represents an alternate approach to develop sterile, reproducible, and long-term protection against malaria. here, we have employed arteether (art), a semi synthetic derivative of artemisinin to explore its potential as a chemoprophylaxis candidate in cps approach and systematically compared the protective potential of arteether with mefloquine, azithromycin and primaquine. blood stage patency and quantita ... | 2016 | 26925772 |
| new orally active diphenylmethyl-based ester analogues of dihydroartemisinin: synthesis and antimalarial assessment against multidrug-resistant plasmodium yoelii nigeriensis in mice. | a new series of ester analogues of artemisinin 8a-f, incorporating diphenylmethyl as pharmacologically privileged substructure, and 8g-j have been prepared and evaluated for their antimalarial activity against multidrug-resistant (mdr) plasmodium yoelii nigeriensis in swiss mice via oral route. these diphenylmethyl-based ester analogues 8a-f were found to be 2-4 folds more active than the antimalarial drugs β-arteether 4 and artesunic acid 5. ester 8a, the most active compound of the series, pro ... | 2016 | 26898813 |
| cross-regulation of two type i interferon signaling pathways in plasmacytoid dendritic cells controls anti-malaria immunity and host mortality. | type i interferon (ifn) is critical for controlling pathogen infection; however, its regulatory mechanisms in plasmacytoid cells (pdcs) still remain unclear. here, we have shown that nucleic acid sensors cgas-, sting-, mda5-, mavs-, or transcription factor irf3-deficient mice produced high amounts of type i ifn-α and ifn-β (ifn-α/β) in the serum and were resistant to lethal plasmodium yoelii ym infection. robust ifn-α/β production was abolished when gene encoding nucleic acid sensor tlr7, signal ... | 2016 | 27793594 |
| sting-licensed macrophages prime type i ifn production by plasmacytoid dendritic cells in the bone marrow during severe plasmodium yoelii malaria. | malaria remains a global health burden causing significant morbidity, yet the mechanisms underlying disease outcomes and protection are poorly understood. herein, we analyzed the peripheral blood of a unique cohort of malawian children with severe malaria, and performed a comprehensive overview of blood leukocytes and inflammatory mediators present in these patients. we reveal robust immune cell activation, notably of cd14+ inflammatory monocytes, nk cells and plasmacytoid dendritic cells (pdcs) ... | 2016 | 27792766 |
| tlr4 and tlr9 signals stimulate protective immunity against blood-stage plasmodium yoelii infection in mice. | the mechanisms regulating the induction of protective immunity against blood-stage malaria remain unclear. resistant dba/2 mouse develops a higher th1 response compared with a susceptible balb/c strain during plasmodium yoelii (py) infection. it is known that the t helper cell response is initiated and polarized by dendritic cells (dcs) of the innate immune system, during which tlr4 and tlr9 are important receptors for the innate recognition of the malaria parasite and its products. we hypothesi ... | 2016 | 27646627 |
| functional characteristics of the gut microbiome in c57bl/6 mice differentially susceptible to plasmodium yoelii. | c57bl/6 mice are widely used for in vivo studies of immune function and metabolism in mammals. in a previous study, it was observed that when c57bl/6 mice purchased from different vendors were infected with plasmodium yoelii, a causative agent of murine malaria, they exhibited both differential immune responses and significantly different parasite burdens: these patterns were reproducible when gut contents were transplanted into gnotobiotic mice. to gain insight into the mechanism of resistance, ... | 2016 | 27729904 |
| increased cd40 expression enhances early sting-mediated type i interferon response and host survival in a rodent malaria model. | both type i interferon (ifn-i) and cd40 play a significant role in various infectious diseases, including malaria and autoimmune disorders. cd40 is mostly known to function in adaptive immunity, but previous observations of elevated cd40 levels early after malaria infection of mice led us to investigate its roles in innate ifn-i responses and disease control. using a plasmodium yoelii nigeriensis n67 and c57bl/6 mouse model, we showed that infected cd40-/- mice had reduced sting and serum ifn-β ... | 2016 | 27716849 |
| probucol dramatically enhances dihydroartemisinin effect in murine malaria. | artemisinin-based combination therapy (act) has been adopted as national policy for the first-line treatment in large number of malaria-endemic regions. however, artemisinin-resistant parasites have emerged and are spreading, with slow-cleaning parasites being reported in patients treated with act. it means that more parasites are exposed to the partner drug alone and the risk of developing resistant parasites against the partner drug is increasing. therefore, the development of a new method to ... | 2016 | 27634686 |
| a recombinant chimeric ad5/3 vector expressing a multistage plasmodium antigen induces protective immunity in mice using heterologous prime-boost immunization regimens. | an ideal malaria vaccine should target several stages of the parasite life cycle and induce antiparasite and antidisease immunity. we have reported a plasmodium yoelii chimeric multistage recombinant protein (p. yoelii linear peptide chimera/recombinant modular chimera), engineered to express several autologous t cell epitopes and sequences derived from the circumsporozoite protein and the merozoite surface protein 1. this chimeric protein elicits protective immunity, mediated by cd4(+) t cells ... | 2016 | 27574299 |
| an atypical splenic b cell progenitor population supports antibody production during plasmodium infection in mice. | hematopoietic stem and progenitor cells (hspcs) function to replenish the immune cell repertoire under steady-state conditions and in response to inflammation due to infection or stress. whereas the bone marrow serves as the primary niche for hematopoiesis, extramedullary mobilization and differentiation of hspcs occur in the spleen during acute plasmodium infection, a critical step in the host immune response. in this study, we identified an atypical hspc population in the spleen of c57bl/6 mic ... | 2016 | 27448588 |
| development of a multi-functional nano-device for safe and effective gene delivery to target organs. | nucleic acids are expected as novel effective medicines, although they require a drug delivery system (dds). complexes of nucleic acids with cationic liposomes and cationic polymers have been mainly used as dds for clinical use. however, most cationic complexes have disadvantages such as strong cytotoxicity and low biocompatibility. we previously found that a plasmid dna (pdna) complex coated with biodegradable γ-polyglutamic acid (γ-pga) provided adequate gene expression without cytotoxicity. b ... | 2016 | 27803485 |
| plasmosep: predicting surface-exposed proteins on the malaria parasite using semisupervised self-training and expert-annotated data. | accurate and comprehensive identification of surface-exposed proteins (seps) in parasites is a key step in developing novel subunit vaccines. however, the reliability of ms-based high-throughput methods for proteome-wide mapping of seps continues to be limited due to high rates of false positives (i.e., proteins mistakenly identified as surface exposed) as well as false negatives (i.e., seps not detected due to low expression or other technical limitations). we propose a framework called plasmos ... | 2016 | 27714937 |
| facilitation through altered resource availability in a mixed-species rodent malaria infection. | a major challenge in disease ecology is to understand how co-infecting parasite species interact. we manipulate in vivo resources and immunity to explain interactions between two rodent malaria parasites, plasmodium chabaudi and p. yoelii. these species have analogous resource-use strategies to the human parasites plasmodium falciparum and p. vivax: p. chabaudi and p. falciparum infect red blood cells (rbc) of all ages (rbc generalist); p. yoelii and p. vivax preferentially infect young rbcs (rb ... | 2016 | 27364562 |
| antimalarial activity of small-molecule benzothiazole hydrazones. | we synthesized a new series of conjugated hydrazones that were found to be active against malaria parasite in vitro, as well as in vivo in a murine model. these hydrazones concentration-dependently chelated free iron and offered antimalarial activity. upon screening of the synthesized hydrazones, compound 5f was found to be the most active iron chelator, as well as antiplasmodial. compound 5f also interacted with free heme (kd [equilibrium dissociation constant] = 1.17 ± 0.8 μm), an iron-contain ... | 2016 | 27139466 |
| marine organism sulfated polysaccharides exhibiting significant antimalarial activity and inhibition of red blood cell invasion by plasmodium. | the antimalarial activity of heparin, against which there are no resistances known, has not been therapeutically exploited due to its potent anticoagulating activity. here, we have explored the antiplasmodial capacity of heparin-like sulfated polysaccharides from the sea cucumbers ludwigothurea grisea and isostichopus badionotus, from the red alga botryocladia occidentalis, and from the marine sponge desmapsamma anchorata. in vitro experiments demonstrated for most compounds significant inhibiti ... | 2016 | 27071342 |
| dynamic control of hepatic plasmodium numbers by hepcidin despite elevated liver iron during iron supplementation. | treatment of iron deficiency anemia in malaria endemic areas is complicated as iron supplementation increases malaria risk while malaria decreases iron absorption. here we measured the influence of hepcidin expression and non-heme iron during iron supplementation on hepatic plasmodium berghei numbers in anemic and non-anemic mice. despite elevated hepatic non-heme iron on the high iron diet, elevated hepcidin expression is associated with less parasite bioavailable iron and lower hepatic parasit ... | 2016 | 26384816 |
| characterization of plasmodium phosphatidylserine decarboxylase expressed in yeast and application for inhibitor screening. | phospholipid biosynthesis is critical for the development, differentiation and pathogenesis of several eukaryotic pathogens. genetic studies have validated the pathway for phosphatidylethanolamine synthesis from phosphatidylserine catalyzed by phosphatidylserine decarboxylase enzymes (psd) as a suitable target for development of antimicrobials; however no inhibitors of this class of enzymes have been discovered. we show that the plasmodium falciparum psd can restore the essential function of the ... | 2016 | 26585333 |
| detailed methodology for high resolution scanning electron microscopy (sem) of murine malaria parasitized-erythrocytes. | scanning electron microscopy (sem) is a powerful tool used to investigate object surfaces and has been widely applied in both material science and biology. with respect to the study of malaria, sem revealed that erythrocytes infected with plasmodium falciparum, a human parasite, display 'knob-like' structures on their surface comprising parasitized proteins. however, detailed methodology for sem studies of malaria parasites is lacking in the literature making such studies challenging. here, we p ... | 2016 | 26987676 |
| one episode of self-resolving plasmodium yoelii infection transiently exacerbates chronic mycobacterium tuberculosis infection. | malaria and tuberculosis (tb) are two of the main causes of death from infectious diseases globally. the pathogenic agents, plasmodium parasites and mycobacterium tuberculosis, are co-endemic in many regions in the world, however, compared to other co-infections like hiv/tb or helminth/tb, malaria/tb has been given less attention both in clinical and immunological studies. due to the lack of sufficient human data, the impact of malaria on tb and vice versa is difficult to estimate but co-infecti ... | 2016 | 26913029 |
| cloning, expression, purification and characterization of plasmodium spp. glyceraldehyde-3-phosphate dehydrogenase. | plasmodium spp. solely rely on glycolysis for their energy needs during asexual multiplication in human rbcs, making the enzymes of this pathway potential drug targets. we have cloned, over-expressed and purified plasmodium falciparum glyceraldehyde-3-phosphate dehydrogenase (pfgapdh) for its kinetic and structural characterization. ∼ 30-40 mg pure recombinant enzyme with a specific activity of 12.6 units/mg could be obtained from a liter of escherichia coli culture. this enzyme is a homotetrame ... | 2016 | 26341815 |
| malaria-cutaneous leishmaniasis co-infection: influence on disease outcomes and immune response. | malaria and cutaneous leishmaniasis (cl) are co-endemic throughout large regions in tropical countries and co-infection may impact the evolution of host-parasite interactions. in the present study, we evaluate malaria/leishmaniasis disease outcome, th1/th2 cytokine levels and the cd4 and cd8 t-cell profiles in a co-infection murine model (balb/c) of plasmodium yoelii 17xnl (py) and leishmania amazonensis (la) or l. braziliensis (lb). malaria parasitaemia was assessed through blood strains staine ... | 2016 | 27446022 |
| nonobese diabetic (nod) mice lack a protective b-cell response against the "nonlethal" plasmodium yoelii 17xnl malaria protozoan. | background. plasmodium yoelii 17xnl is a nonlethal malaria strain in mice of different genetic backgrounds including the c57bl/6 mice (i-a(b)/i-e(null)) used in this study as a control strain. we have compared the trends of blood stage infection with the nonlethal murine strain of p. yoelii 17xnl malaria protozoan in immunocompetent nonobese diabetic (nod) mice prone to type 1 diabetes (t1d) and c57bl/6 mice (control mice) that are not prone to t1d and self-cure the p. yoelii 17xnl infection. pr ... | 2016 | 28074170 |
| plasmodium yoelii nigeriensis (n67) is a robust animal model to study malaria transmission by south american anopheline mosquitoes. | malaria is endemic in the american continent and the amazonian rainforest is the region with the highest risk of transmission. however, the lack of suitable experimental models to infect malaria vectors from the americas has limited the progress to understand the biology of transmission in this region. anopheles aquasalis, a major vector in coastal areas of south america, was found to be highly refractory to infection with two strains of plasmodium falciparum (nf54 and 7g8) and with plasmodium b ... | 2016 | 27911924 |
| effects of transmission-blocking vaccines simultaneously targeting pre- and post-fertilization antigens in the rodent malaria parasite plasmodium yoelii. | transmission-blocking vaccine (tbv) is a promising strategy for interrupting the malaria transmission cycle. current tbv candidates include both pre- and post-fertilization antigens expressed during sexual development of the malaria parasites. | 2016 | 27502144 |
| in vitro analysis of the interaction between atovaquone and proguanil against liver stage malaria parasites. | the interaction between atovaquone and proguanil has never been studied against liver stage malaria, which is the main target of this drug combination when used for chemoprevention. using human hepatocytes lacking cytochrome p450 activity, and thus avoiding proguanil metabolizing into potent cycloguanil, we show in vitro that the atovaquone-proguanil combination synergistically inhibits the growth of rodent plasmodium yoelii parasites. these results provide a pharmacological basis for the high e ... | 2016 | 26926628 |
| a plasmodium promiscuous t cell epitope delivered within the ad5 hexon protein enhances the protective efficacy of a protein based malaria vaccine. | a malaria vaccine is a public health priority. in order to produce an effective vaccine, a multistage approach targeting both the blood and the liver stage infection is desirable. the vaccine candidates also need to induce balanced immune responses including antibodies, cd4+ and cd8+ t cells. protein-based subunit vaccines like rts,s are able to induce strong antibody response but poor cellular reactivity. adenoviral vectors have been effective inducing protective cd8+ t cell responses in severa ... | 2016 | 27128437 |
| co-administration of α-galcer analog and tlr4 agonist induces robust cd8(+) t-cell responses to pycs protein and wt-1 antigen and activates memory-like effector nkt cells. | in the present study, the combined adjuvant effect of 7dw8-5, a potent α-galcer-analog, and monophosphoryl lipid a (mpla), a tlr4 agonist, on the induction of vaccine-induced cd8(+) t-cell responses and protective immunity was evaluated. mice were immunized with peptides corresponding to the cd8(+) t-cell epitopes of a malaria antigen, a circumsporozoite protein of plasmodium yoelii, and a tumor antigen, a wilms tumor antigen-1 (wt-1), together with 7dw8-5 and mpla, as an adjuvant. these immuniz ... | 2016 | 27132023 |
| defining rules of cd8(+) t cell expansion against pre-erythrocytic plasmodium antigens in sporozoite-immunized mice. | whole plasmodium sporozoites serve as both experimental tools and potentially as deployable vaccines in the fight against malaria infection. live sporozoites infect hepatocytes and induce a diverse repertoire of cd8(+) t cell responses, some of which are capable of killing plasmodium-infected hepatocytes. previous studies in plasmodium yoelii-immunized balb/c mice showed that some cd8(+) t cell responses expanded with repeated parasite exposure, whereas other responses did not. | 2016 | 27113469 |
| a plasmodium yoelii mei2-like rna binding protein is essential for completion of liver stage schizogony. | plasmodium parasites employ posttranscriptional regulatory mechanisms as their life cycle transitions between host cell invasion and replication within both the mosquito vector and mammalian host. rna binding proteins (rbps) provide one mechanism for modulation of rna function. to explore the role of plasmodium rbps during parasite replication, we searched for rbps that might play a role during liver stage development, the parasite stage that exhibits the most extensive growth and replication. w ... | 2016 | 26883588 |
| enhanced transmission of malaria parasites to mosquitoes in a murine model of type 2 diabetes. | more than half of the world's population is at risk of malaria and simultaneously, many malaria-endemic regions are facing dramatic increases in the prevalence of type 2 diabetes. studies in murine malaria models have examined the impact of malaria infection on type 2 diabetes pathology, it remains unclear how this chronic metabolic disorder impacts the transmission of malaria. in this report, the ability type 2 diabetic rodents infected with malaria to transmit parasites to anopheles stephensi ... | 2016 | 27102766 |
| a highly infectious plasmodium yoelii parasite, bearing plasmodium falciparum circumsporozoite protein. | plasmodium circumsporozoite protein (csp) is a major surface antigen present in the sporozoite (spz) stage of a malaria parasite. rts, s vaccine, the most clinically advanced malaria vaccine, consists of a large portion of plasmodium falciparum csp (pfcsp). a highly infectious, recombinant rodent malaria, plasmodium yoelii parasite bearing a full-length pfcsp, pfcsp/py spz, was needed as a tool to evaluate the role of pfcsp in mediating, protective, anti-malaria immunity in a mouse model. | 2016 | 27068454 |
| the tlr2 is activated by sporozoites and suppresses intrahepatic rodent malaria parasite development. | tlrs (toll-like receptors) play an important role in the initiation of innate immune responses against invading microorganisms. although several tlrs have been reported to be involved in the innate immune response against the blood-stage of malaria parasites, the role of tlrs in the development of the pre-erythrocytic stage is still largely unknown. here, we found that sporozoite and its lysate could significantly activate the tlr2, and induce macrophages to release proinflammatory cytokines, in ... | 2015 | 26667391 |
| co-expression of interleukin-15 enhances the protective immune responses induced by immunization with a murine malaria mva-based vaccine encoding the circumsporozoite protein. | malaria remains a major global public health problem with an estimated 200 million cases detected in 2012. although the most advanced candidate malaria vaccine (rts,s) has shown promise in clinical trials, its modest efficacy and durability have created uncertainty about the impact of rts,s immunization (when used alone) on global malaria transmission. here we describe the development and characterization of a novel modified vaccinia virus ankara (mva)-based malaria vaccine which co-expresses th ... | 2015 | 26505634 |
| plasmodium suppresses expansion of t cell responses to heterologous infections. | plasmodium remains a major pathogen causing malaria and impairing defense against other infections. defining how plasmodium increases susceptibility to heterologous pathogens may lead to interventions that mitigate the severity of coinfections. previous studies proposed that reduced t cell responses during coinfections are due to diminished recruitment of naive t cells through infection-induced decreases in chemokine ccl21. we found that, although listeria infections reduced expression of ccl21 ... | 2015 | 25505280 |
| phagosomal acidification prevents macrophage inflammatory cytokine production to malaria, and dendritic cells are the major source at the early stages of infection: implication for malaria protective immunity development. | inflammatory cytokines produced at the early stages of malaria infection contribute to shaping protective immunity and pathophysiology. to gain mechanistic insight into these processes, it is important to understand the cellular origin of cytokines because both cytokine input and cytokine-producing cells play key roles. here, we determined cytokine responses by monocytes, macrophages, and dendritic cells (dcs) to purified plasmodium falciparum and plasmodium berghei anka, and by spleen macrophag ... | 2015 | 26240140 |
| immunization of mice with plasmodium tctp delays establishment of plasmodium infection. | translationally controlled tumour protein (tctp) may play an important role in the establishment or maintenance of parasitemia in a malarial infection. in this study, the potential of tctp as a malaria vaccine was investigated in two trials. in the initial vaccine trial, plasmodium falciparum tctp (pftctp) was expressed in saccharomyces cerevisiae and used to immunize balb/c mice. following challenge with plasmodium yoelii ym, parasitemia was significantly reduced during the early stages of infe ... | 2015 | 25376500 |
| detection of plasmodium berghei and plasmodium yoelii liver-stage parasite burden by quantitative real-time pcr. | direct detection and quantification of liver-stage plasmodium parasites became possible with the development of quantitative real-time pcr (qpcr). here we describe the measurement of parasite burden in the livers of mice infected with the rodent malaria species, plasmodium berghei and plasmodium yoelii. this method is based on detection of expression of parasite ribosomal 18s rna and can serve as an endpoint to accurately evaluate the efficacy of vaccines targeting the preerythrocytic stages of ... | 2015 | 26450381 |
| characterization of liver cd8 t cell subsets that are associated with protection against pre-erythrocytic plasmodium parasites. | murine models of malaria, such as plasmodium berghei (pb) and plasmodium yoelii (py), have been used for decades to identify correlates of protection associated with immunization using radiation-attenuated sporozoites (ras). to date, ras is the only known immunization regimen to consistently deliver 100 % sterilizing immunity and is considered the "gold standard" of protection against malaria. the ability to isolate lymphocytes directly from the liver of immune mice has facilitated the identific ... | 2015 | 26450377 |
| probucol-induced α-tocopherol deficiency protects mice against malaria infection. | the emergence of malaria pathogens having resistance against antimalarials implies the necessity for the development of new drugs. recently, we have demonstrated a resistance against malaria infection of α-tocopherol transfer protein knockout mice showing undetectable plasma levels of α-tocopherol, a lipid-soluble antioxidant. however, dietary restriction induced α-tocopherol deficiency is difficult to be applied as a clinical antimalarial therapy. here, we report on a new strategy to potentiall ... | 2015 | 26296197 |
| colocalization of a cd1d-binding glycolipid with a radiation-attenuated sporozoite vaccine in lymph node-resident dendritic cells for a robust adjuvant effect. | a cd1d-binding glycolipid, α-galactosylceramide (αgalcer), activates invariant nk t cells and acts as an adjuvant. we previously identified a fluorinated phenyl ring-modified αgalcer analog, 7dw8-5, displaying nearly 100-fold stronger cd1d binding affinity. in the current study, 7dw8-5 was found to exert a more potent adjuvant effect than αgalcer for a vaccine based on radiation-attenuated sporozoites of a rodent malaria parasite, plasmodium yoelii, also referred to as irradiated p. yoelii sporo ... | 2015 | 26254338 |
| l-arginine supplementation in mice enhances no production in spleen cells and inhibits plasmodium yoelii transmission in mosquitoes. | the life cycle of plasmodium is complex, requiring invasion of two different hosts, humans and mosquitoes. in humans, initiation of an effective th1 response during early infection is critical for the control of parasite multiplication. in mosquitoes, inhibition of the development of sexual-stage parasites interrupts the parasite transmission. in this study, we aim to investigate whether dietary supplementation of l-arginine (l-arg) in mice affects plasmodium yoelii 17xl (py17xl) transmission in ... | 2015 | 26070945 |
| mechanisms of stage-transcending protection following immunization of mice with late liver stage-arresting genetically attenuated malaria parasites. | malaria, caused by plasmodium parasite infection, continues to be one of the leading causes of worldwide morbidity and mortality. development of an effective vaccine has been encumbered by the complex life cycle of the parasite that has distinct pre-erythrocytic and erythrocytic stages of infection in the mammalian host. historically, malaria vaccine development efforts have targeted each stage in isolation. an ideal vaccine, however, would target multiple life cycle stages with multiple arms of ... | 2015 | 25974076 |
| chloroquine neither eliminates liver stage parasites nor delays their development in a murine chemoprophylaxis vaccination model. | chemoprophylaxis vaccination (cvac) confers long lasting sterile protection against homologous parasite strains in humans, and involves inoculation of infectious sporozoites (spz) under drug cover. cvac using the drug chloroquine (cq) induces pre-erythrocytic immunity in humans that includes antibody to spz and t-cell responses to liver stage (ls) parasites. the mechanism by which cvac with cq induces strong protective immunity is not understood as untreated infections do not confer protection. ... | 2015 | 25914686 |
| cyclic gmp balance is critical for malaria parasite transmission from the mosquito to the mammalian host. | transmission of malaria occurs during anopheles mosquito vector blood meals, when plasmodium sporozoites that have invaded the mosquito salivary glands are delivered to the mammalian host. sporozoites display a unique form of motility that is essential for their movement across cellular host barriers and invasion of hepatocytes. while the molecular machinery powering motility and invasion is increasingly well defined, the signaling events that control these essential parasite activities have not ... | 2015 | 25784701 |
| regulation of plasmodium yoelii oocyst development by strain- and stage-specific small-subunit rrna. | one unique feature of malaria parasites is the differential transcription of structurally distinct rrna (rrna) genes at different developmental stages: the a-type genes are transcribed mainly in asexual stages, whereas the s-type genes are expressed mostly in sexual or mosquito stages. conclusive functional evidence of different rrnas in regulating stage-specific parasite development, however, is still absent. here we performed genetic crosses of plasmodium yoelii parasites with one parent havin ... | 2015 | 25759501 |
| a sufficient role of mhc class i molecules on hepatocytes in anti-plasmodial activity of cd8 (+) t cells in vivo. | although cd8(+) t cells are shown to mediate the protective immunity against the liver stages of malaria parasites in mice, whether the direct presentation of malaria antigen by major histocompatibility complex (mhc) class i molecules expressed on the liver of infected host is required for anti-plasmodial activity of cd8(+) t cells is still unknown. presently, there is only one cd8(+) epitope, syvpsaeqi, derived from the circumsporozoite protein of plasmodium yoelii (pycs), that mediates anti-ma ... | 2015 | 25729379 |
| within-host competition does not select for virulence in malaria parasites; studies with plasmodium yoelii. | in endemic areas with high transmission intensities, malaria infections are very often composed of multiple genetically distinct strains of malaria parasites. it has been hypothesised that this leads to intra-host competition, in which parasite strains compete for resources such as space and nutrients. this competition may have repercussions for the host, the parasite, and the vector in terms of disease severity, vector fitness, and parasite transmission potential and fitness. it has also been a ... | 2015 | 25658331 |
| cd40 is required for protective immunity against liver stage plasmodium infection. | the costimulatory molecule cd40 enhances immunity through several distinct roles in t cell activation and t cell interaction with other immune cells. in a mouse model of immunity to liver stage plasmodium infection, cd40 was critical for the full maturation of liver dendritic cells, accumulation of cd8(+) t cells in the liver, and protective immunity induced by immunization with the plasmodium yoelii fabb/f(-) genetically attenuated parasite. using mixed adoptive transfers of polyclonal wild-typ ... | 2015 | 25646303 |
| interactions between a fungal entomopathogen and malaria parasites within a mosquito vector. | mosquitoes are becoming increasingly resistant to the chemical insecticides currently available for malaria vector control, spurring interest in alternative management tools. one promising technology is the use of fungal entomopathogens. fungi have been shown to impact the potential for mosquitoes to transmit malaria by reducing mosquito longevity and altering behaviour associated with flight and host location. additionally, fungi could impact the development of malaria parasites within the mosq ... | 2015 | 25626485 |
| dried whole-plant artemisia annua slows evolution of malaria drug resistance and overcomes resistance to artemisinin. | pharmaceutical monotherapies against human malaria have proven effective, although ephemeral, owing to the inevitable evolution of resistant parasites. resistance to two or more drugs delivered in combination will evolve more slowly; hence combination therapies have become the preferred norm in the fight against malaria. at the forefront of these efforts has been the promotion of artemisinin combination therapy, but despite these efforts, resistance to artemisinin has begun to emerge. in 2012, w ... | 2015 | 25561559 |
| immunogenicity and protective potential of a plasmodium spp. enolase peptide displayed on archaeal gas vesicle nanoparticles. | plasmodium falciparum enolase has been shown to localize on the surface of merozoites and ookinetes. immunization of mice with recombinant plasmodium enolase (rpfeno) showed partial protection against malaria. anti-rpfeno antibodies inhibited growth of the parasite in in vitro cultures and blocked ookinete invasion of mosquito midgut epithelium. it is hypothesized that parasite specific moonlighting functions (e.g. host cell invasion) may map on to unique structural elements of pfeno. since enol ... | 2015 | 26463341 |
| il-18-induced expression of high-affinity il-2r on murine nk cells is essential for nk-cell ifn-γ production during murine plasmodium yoelii infection. | early production of pro-inflammatory cytokines, including ifn-γ, is essential for control of blood-stage malaria infections. we have shown that ifn-γ production can be induced among human natural killer (nk) cells by coculture with plasmodium falciparum infected erythrocytes, but the importance of this response is unclear. to further explore the role of nk cells during malaria infection, we have characterized the nk-cell response of c57bl/6 mice during lethal (pyym) or nonlethal (py17xnl) p. yoe ... | 2015 | 26420375 |
| transient loss of protection afforded by a live attenuated non-typhoidal salmonella vaccine in mice co-infected with malaria. | in immunocompetent individuals, non-typhoidal salmonella serovars (nts) are associated with gastroenteritis, however, there is currently an epidemic of nts bloodstream infections in sub-saharan africa. plasmodium falciparum malaria is an important risk factor for invasive nts bloodstream in african children. here we investigated whether a live, attenuated salmonella vaccine could be protective in mice, in the setting of concurrent malaria. surprisingly, mice acutely infected with the nonlethal m ... | 2015 | 26366739 |
| in silico identification of genetically attenuated vaccine candidate genes for plasmodium liver stage. | genetically attenuated parasites (gaps) that lack genes essential for the liver stage of the malaria parasite, and therefore cause developmental arrest, have been developed as live vaccines in rodent malaria models and recently been tested in humans. the genes targeted for deletion were often identified by trial and error. here we present a systematic gene - protein and transcript - expression analyses of several plasmodium species with the aim to identify candidate genes for the generation of n ... | 2015 | 26348884 |
| in vivo curative and protective potential of orally administered 5-aminolevulinic acid plus ferrous ion against malaria. | 5-aminolevulinic acid (ala) is a naturally occurring amino acid present in diverse organisms and a precursor of heme biosynthesis. ala is commercially available as a component of cosmetics, dietary supplements, and pharmaceuticals for cancer diagnosis and therapy. recent reports demonstrated that the combination of ala and ferrous ion (fe(2+)) inhibits the in vitro growth of the human malaria parasite plasmodium falciparum. to further explore the potential application of ala and ferrous ion as a ... | 2015 | 26324278 |
| discovery of new thienopyrimidinone derivatives displaying antimalarial properties toward both erythrocytic and hepatic stages of plasmodium. | a preliminary in vitro screening of compounds belonging to various chemical families from our library revealed the thieno[3,2-d]pyrimidin-4(3h)-one scaffold displayed a promising profile against plasmodium falciparum. then, 120 new derivatives were synthesized and evaluated in vitro; compared to drug references, 40 showed good activity toward chloroquine sensitive (ic50 35-344 nm) and resistant (ic50 45-800 nm) p. falciparum strains. they were neither cytotoxic (cc50 15-50 μm) toward hepg2 and c ... | 2015 | 25791675 |
| the rodent malaria lactate dehydrogenase assay provides a high throughput solution for in vivo vaccine studies. | rodent malaria is a useful model for evaluating the efficacy of malaria vaccine candidates; however, labor-intensive microscopic parasite counting hampers the use of an in vivo parasite challenge in high-throughput screening. the measurement of malaria parasite lactate dehydrogenase (pldh) activity, which is commonly used in the in vitro growth inhibition assay of plasmodium falciparum, may be the cheapest and simplest alternative to microscopic parasite counting. however, the pldh assay has not ... | 2015 | 25701649 |
| humoral immune responses to a recombinant plasmodium vivax tryptophan-rich antigen among plasmodium vivax-infected patients and its localization in the parasite. | our recent studies have focused on the identification and characterization of the tryptophan-rich proteins of the plasmodium vivax parasite where their role in the elicitation of humoral and cellular responses and erythrocyte-binding activity was investigated. here, we report the humoral responses of a 32.4-kda p. vivax tryptophan-rich antigen (pvtrag32.4) among the sera of p. vivax-infected patients. pvtrag32.4 also contains an unusually high percentage of tryptophan residues (10.7 %) that are ... | 2015 | 25467946 |
| dendritic cells subsets mediated immune response during plasmodium berghei anka and plasmodium yoelii infection. | the roles of dendritic cells (dcs) in mediating immunity against plasmodium infection have been extensively investigated, but immune response during pathogenesis of malaria is still poorly understood. in the present study, we compared the splenic dcs phenotype and function during p. berghei anka (pba) or p. yoelii (p. yoelii) infection in swiss mice. we observed that pba-infected mice developed more myeloid and mature dcs capable of secreting il-12, while p. yoelii-infected mice had more plasmac ... | 2015 | 25792277 |
| host erythrocyte environment influences the localization of exported protein 2, an essential component of the plasmodium translocon. | malaria parasites replicating inside red blood cells (rbcs) export a large subset of proteins into the erythrocyte cytoplasm to facilitate parasite growth and survival. ptex, the parasite-encoded translocon, mediates protein transport across the parasitophorous vacuolar membrane (pvm) in plasmodium falciparum-infected erythrocytes. proteins exported into the erythrocyte cytoplasm have been localized to membranous structures, such as maurer's clefts, small vesicles, and a tubovesicular network. c ... | 2015 | 25662767 |
| in vitro alterations do not reflect a requirement for host cell cycle progression during plasmodium liver stage infection. | prior to invading nonreplicative erythrocytes, plasmodium parasites undergo their first obligate step in the mammalian host inside hepatocytes, where each sporozoite replicates to generate thousands of merozoites. while normally quiescent, hepatocytes retain proliferative capacity and can readily reenter the cell cycle in response to diverse stimuli. many intracellular pathogens, including protozoan parasites, manipulate the cell cycle progression of their host cells for their own benefit, but i ... | 2015 | 25416236 |
| isolation of invasive plasmodium yoelii merozoites with a long half-life to evaluate invasion dynamics and potential invasion inhibitors. | malaria symptoms and pathogenesis are caused by blood stage parasite burdens of plasmodium spp., for which invasion of red blood cells (rbcs) by merozoites is essential. successful targeting by either drugs or vaccines directed against the whole merozoite or its antigens during its transient extracellular status would contribute to malaria control by impeding rbc invasion. to understand merozoite invasion biology and mechanisms, it is desired to obtain merozoites that retain their invasion activ ... | 2015 | 26684675 |