| generation of tissue-specific h-2kd transgenic mice for the study of k(d)-restricted malaria epitope-specific cd8+ t-cell responses in vivo. | cd8(+) t cells are critical for the control of various intracellular infections and cancers. to date, however, effective t cell-based vaccines remain elusive, due, in part, to the lack of in vivo models that facilitate the dissection of antigen-specific cd8(+) t-cell responses primed by different antigen-presenting cells (apcs). in this study, we generated four lines of h-2k(d) transgenic (k(d) tg) mice that differed in their expression of h-2k(d): dendritic cells (dcs) only (cd11c-k(d)), macrop ... | 2013 | 23142461 |
| age-related susceptibility and resistance to nonlethal plasmodium yoelii infection in c57bl/6 mice. | in cases of human malaria, children suffer very high rates of morbidity and mortality. to analyse the mechanisms involved in age-dependent protection against malaria, we investigated the characterization of immune responses to plasmodium yoelii 17xnl (p.y 17xnl) in young (3 weeks) and middle-aged (8 months) c57bl/6 mice. in this study, we found that 100% of young mice succumbed to p.y 17xnl infection with higher parasitemia, while middle-aged mice were able to clear blood parasites and no mortal ... | 2012 | 23136794 |
| optimized protocols for improving the likelihood of cloning recombinant progeny from plasmodium yoelii genetic crosses. | genetic cross is a powerful tool for studying malaria genes contributing to drug resistance, parasite development, and pathogenesis. cloning and identification of recombinant progeny (rp) is laborious and expensive, especially when a large proportion of progeny derived from self-fertilization are present in the uncloned progeny of a genetic cross. since the frequency of cross-fertilization affects the number of recombinant progeny in a genetic cross, it is important to optimize the procedure of ... | 2013 | 23116600 |
| on designing stable magnetic vectors as carriers for malaria dna vaccine. | superparamagnetic iron oxide nanoparticles (spions) can be used as therapeutic and diagnostic agents due to their unique magnetic characteristics, provided that they are stable in physiological conditions. here, the assembly of different magnetic vector configurations comprising spions, polyethylenimine (pei), and hyaluronic acid (ha), acting as carriers for malaria dna vaccine encoding plasmodium yoelii merozoite surface protein msp1-19 (vr1020-pymsp1-19), and their stability in different cell ... | 2013 | 23104020 |
| implication of glutathione in the in vitro antiplasmodial mechanism of action of ellagic acid. | the search for new antimalarial chemotherapy has become increasingly urgent due to parasite resistance to current drugs. ellagic acid (ea) is a polyphenol, recently found in various plant products, that has effective antimalarial activity in vitro and in vivo without toxicity. to further understand the antimalarial mechanism of action of ea in vitro, we evaluated the effects of ea, ascorbic acid and n-acetyl-l-cysteine (nac), alone and/or in combination on the production of reactive oxygen speci ... | 2012 | 23029306 |
| t cell responses induced by adenoviral vectored vaccines can be adjuvanted by fusion of antigen to the oligomerization domain of c4b-binding protein. | viral vectored vaccines have been shown to induce both t cell and antibody responses in animals and humans. however, the induction of even higher level t cell responses may be crucial in achieving vaccine efficacy against difficult disease targets, especially in humans. here we investigate the oligomerization domain of the α-chain of c4b-binding protein (c4 bp) as a candidate t cell "molecular adjuvant" when fused to malaria antigens expressed by human adenovirus serotype 5 (adhu5) vectored vacc ... | 2012 | 22984589 |
| malaria infection alters the expression of b-cell activating factor resulting in diminished memory antibody responses and survival. | malaria is a major cause of morbidity worldwide with reports of over 200-500 million infected individuals and nearly 1 million deaths each year. antibodies have been shown to play a critical role in controlling the blood stage of this disease; however, in malaria-endemic areas antibody immunity is slow to develop despite years of exposure to plasmodium spp. the causative parasite. using rodent plasmodium yoelii ym, we provide evidence that malarial infections result in a decrease in the proporti ... | 2012 | 22936176 |
| allicin enhances host pro-inflammatory immune responses and protects against acute murine malaria infection. | during malaria infection, multiple pro-inflammatory mediators including ifn-γ, tnf and nitric oxide (no) play a crucial role in the protection against the parasites. modulation of host immunity is an important strategy to improve the outcome of malaria infection. allicin is the major biologically active component of garlic and shows anti-microbial activity. allicin is also active against protozoan parasites including plasmodium, which is thought to be mediated by inhibiting cysteine proteases. i ... | 2012 | 22873687 |
| supplement of l-arg improves protective immunity during early-stage plasmodium yoelii 17xl infection. | l-arginine (l-arg), the precursor of nitric oxide (no), plays multiple important roles in nutrient metabolism and immune regulation. l-arg supplement serves as a potential adjunctive therapy for severe malaria, because it improves no bioavailability and reverses endothelial dysfunction in severe malaria patients. in this study, we investigated the effect of dietary l-arg supplement on host immune responses during subsequent malaria infection using the plasmodium yoelii 17xl - balb/c mouse model. ... | 2013 | 22709481 |
| qsar, docking and admet studies of artemisinin derivatives for antimalarial activity targeting plasmepsin ii, a hemoglobin-degrading enzyme from p. falciparum. | this work presents the development of quantitative structure activity relationship (qsar) model to predict the antimalarial activity of artemisinin derivatives. the structures of the molecules are represented by chemical descriptors that encode topological, geometric, and electronic structure features. screening through qsar model suggested that compounds a24, a24a, a53, a54, a62 and a64 possess significant antimalarial activity. linear model is developed by the multiple linear regression method ... | 2012 | 22670592 |
| plasmodium yoelii blood-stage antigens newly identified by immunoaffinity using purified igg antibodies from malaria-resistant mice. | as the search for an effective human malaria vaccine continues, understanding immune responses to plasmodium in rodent models is perhaps the key to unlocking new vaccine strategies. the recruitment of parasite-specific antibodies is an important component of natural immunity against infection in blood-stage malaria. here, we describe the use of sera from naturally surviving icr mice after infection with lethal doses of plasmodium yoelii yoelii 17xl to identify highly immunogenic blood-stage anti ... | 2012 | 22658767 |
| efficient control of plasmodium yoelii infection in balb/c and c57bl/6 mice with pre-existing strongyloides ratti infection. | about 225 million malaria cases have been reported worldwide in 2009, and one-third of the world's population is infected with parasitic helminths. as helminths and plasmodium are co-endemic, concurrent infections frequently occur. helminths have been shown to modulate the host's immune response; therefore, pre-existing helminth infections may interfere with the efficient immune response to plasmodium. to study the interaction between helminths and plasmodium, we established a murine model of co ... | 2012 | 22554071 |
| strong impact of cd4+ foxp3+ regulatory t cells and limited effect of t cell-derived il-10 on pathogen clearance during plasmodium yoelii infection. | it is well established that cd4(+)cd25(+)foxp3(+) regulatory t cells (tregs) play a crucial role in the course of different infectious diseases. however, contradictory results have been published regarding to malaria infection. in this study, we report that specific ablation of foxp3(+) tregs in plasmodium yoelii-infected dereg-balb/c mice leads to an increase in t cell activation accompanied by a significant decrease in parasitemia. to better understand how foxp3(+) tregs orchestrate this pheno ... | 2012 | 22544931 |
| tlr9 and myd88 are crucial for the development of protective immunity to malaria. | effective resolution of malaria infection by avoiding pathogenesis requires regulated pro- to anti-inflammatory responses and the development of protective immunity. tlrs are known to be critical for initiating innate immune responses, but their roles in the regulation of immune responses and development of protective immunity to malaria remain poorly understood. in this study, using wild-type, tlr2(-/-), tlr4(-/-), tlr9(-/-), and myd88(-/-) mice infected with plasmodium yoelii, we show that tlr ... | 2012 | 22516959 |
| expression of non-tlr pattern recognition receptors in the spleen of balb/c mice infected with plasmodium yoelii and plasmodium chabaudi chabaudi as. | the spleen plays a crucial role in the development of immunity to malaria, but the role of pattern recognition receptors (prrs) in splenic effector cells during malaria infection is poorly understood. in the present study, we analysed the expression of selected prrs in splenic effector cells from balb/c mice infected with the lethal and non-lethal plasmodium yoelii strains 17xl and 17x, respectively, and the non-lethal plasmodium chabaudi chabaudi as strain. the results of these experiments show ... | 2012 | 22510838 |
| the course of a primary infection of plasmodium yoelii 17xl in both 129s1 and ifn-γ receptor-deficient mice. | in the present study, we found that 129s1 mice are resistant to the infection with plasmodium yoelii 17xl, which is highly virulent and causes lethal infection in various strains of mice. in contrast, ifn-γ receptor-deficient (ifn-γr(-/-)) mice on the 129s1 background were much more susceptible than 129s1 mice with intraperitoneal infection with 1 × 10(5) parasitized erythrocytes. the mortality in 129s1 and ifn-γr(-/-) mice was 11.6 and 79.4 %, respectively. following inoculation of the parasite ... | 2012 | 22392138 |
| anti-malarial activity of geldanamycin derivatives in mice infected with plasmodium yoelii. | geldanamycin (ga), a benzoquinone ansamycin antibiotic has been shown in vitro to possess anti-plasmodial activity. pharmacological activity of this drug is attributed to its ability to inhibit pfhsp90. the parasite growth arrest has been shown to be due to drug-induced blockage of the transition from ring to trophozoite stage. to further evaluate the consequences of this pharmacodynamic feature, the anti-malarial activity of ga analogs with enhanced drug properties in a plasmodium-infected anim ... | 2012 | 22361388 |
| induction of ssdna-binding autoantibody secreting b cell immunity during murine malaria infection is a critical part of the protective immune responses. | although it has been hypothesized that autoimmune-like phenomena may play a critical role in the protective immune responses to both human and animal malaria, there are still no evidence-based data to support this view. in this study we demonstrate that the majority of anti-single stranded (ss) dna autoantibody secreting b cells were confined to b220(+)cd21(+)cd23(-) cells and that these cells expanded significantly in the spleen of c57bl/6 mice infected with plasmodium yoelii 17x non-lethal (py ... | 2013 | 22361243 |
| polysaccharides from the chinese medicinal herb achyranthes bidentata enhance anti-malarial immunity during plasmodium yoelii 17xl infection in mice. | clinical immunity to malaria in human populations is developed after repeated exposure to malaria. regulation and balance of host immune responses may lead to optimal immunity against malaria parasite infection. polysaccharides (abps) derived from the chinese herb ox knee achyranthes bidentata possess immuno-modulatory functions. the aim of this study is to use the rodent malaria model plasmodium yoelii 17xl (p. y17xl) to examine whether pretreatment with abps will modulate host immunity against ... | 2012 | 22348301 |
| intravital microscopy of the spleen: quantitative analysis of parasite mobility and blood flow. | the advent of intravital microscopy in experimental rodent malaria models has allowed major advances to the knowledge of parasite-host interactions. thus, in vivo imaging of malaria parasites during pre-erythrocytic stages have revealed the active entrance of parasites into skin lymph nodes, the complete development of the parasite in the skin, and the formation of a hepatocyte-derived merosome to assure migration and release of merozoites into the blood stream. moreover, the development of indi ... | 2012 | 22298018 |
| roles of the duffy antigen and glycophorin a in malaria infectionand erythrocyte. | we constructed gene knockout mice lacking either the duffy antigen (dfy) or glycophorin a (gpa), major glycoproteins that are expressed on erythrocyte membranes, to examine the role of these proteins in malaria infection and erythrocyte. all of the rodent malarias examined proliferated in the erythrocytes of these knockout mice, indicating that neither the duffy antigen nor gpa has an essential role as a receptor for malaria parasites. duffy antigen knockout mice infected by plasmodium yoelii 17 ... | 2008 | 22504500 |
| 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 |