Publications
| Title | Abstract | Year(sorted ascending) Filter | PMID Filter |
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| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |