Toll-like receptors(TLRs) are a central component of innate immune system and play a major role as the initiator of the innate immune responses to defend against bacteria,viruses,parasite and other pathogens.During ma...Toll-like receptors(TLRs) are a central component of innate immune system and play a major role as the initiator of the innate immune responses to defend against bacteria,viruses,parasite and other pathogens.During malaria infection,TLRs signaling pathways are initialed with the recognition of Plasmodium glycosylphosphatidylinositols(GPI) and hemozoin as pathogen-associated molecular patterns(PAMPs).And then,activation of TLRs signaling induces specific biological responses against malaria parasites invasion.However,TLRs are also involved in malaria pathogenesis and enhancement of immune tolerance and evasion for malaria infection.Moreover,malaria parasites regulate selectively TLRs expression on immune cells.Thus,these evidences indicated that TLRs have contrary roles on malaria infection.Understanding the complicated roles of TLRs on malaria infection will contribute us to design more effective anti-malaria drugs or vaccines.展开更多
We have previously demonstrated the ability of malaria parasites to interfere with specific immune responses. CD4 T cells specific to parasite antigens, but not CD4 T cells specific to an irrelevant antigen, ovalbumin...We have previously demonstrated the ability of malaria parasites to interfere with specific immune responses. CD4 T cells specific to parasite antigens, but not CD4 T cells specific to an irrelevant antigen, ovalbumin (OVA), are de- leted via apoptosis during malaria infection. It is of interest, therefore, to investigate the immune responses that developed following vaccination with the 19 kDa carboxylterminus of the merozoite surface protein 1 (MSP119) in mice that had previ- ously experienced malaria infection. In this study, pre-exposure of mice to Plasmodium yoelii elicited native anti-MSP119 an- tibody responses, which could be boosted by vaccination with recombinant MSP119 . likewise, infection of MSP119-primed mice with Plasmodium yoelii ( P . yoelii) led to an increase of anti-MSP119 antibodies. MSP119 vaccination of malaria pre- exposed mice or immunization by infection/cure of MSP119-primed mice enabled the mice to survive challenge infection, with the former group having slightly lower parasitaemia. The data suggest that exposure to malaria infection primes a natural im- mune response which can be boosted by vaccination. This information is relevant to the development of a vaccine for use in individuals living in malaria-endemic areas.展开更多
Both eukaryotic and prokaryotic pathogens infect the host stably via an immune evasion mecha- nism termed mutually exclusive expression. Nowadays, little is known about this epigenetic mechanism, largely limiting th...Both eukaryotic and prokaryotic pathogens infect the host stably via an immune evasion mecha- nism termed mutually exclusive expression. Nowadays, little is known about this epigenetic mechanism, largely limiting the understanding of pathogenesis of many bacterial, fungal and protozoan pathogens and therefore the development of novel drugs and vaccines. In the most severe malaria parasite, Plasrnodiurn falciparum, there is a major virulence gene family termed vat, by which the variant antigen PfEMP1 is encoded and expressed on the surface of parasite-infected erythrocytes. Each parasite carries about 60 anti- genically various vat genes, however, only one of which is expressed at a given time during infection. P. falciparum expresses PfEMP1s in this clonally variant manner to bind to different human endothelial re- ceptors, allowing the infected erythrocytes to sequester in tissues to escape the host＇s immune response in- cluding spleen killing and humoral immunity. At present, the mechanism of mutually exclusive expression of the var gene family remains largely unknown, even though there is increasing evidence suggesting im- portant roles of the epigenetic regulation involved in vat gene expression. In addition, epigenetic factors were also found in association with transcriptional regulation of other antigenic variant gene families in P. falciparum. In this paper, we review the current understanding of epigenetic regulations of P. falcipa- rum virulence genes with particular views toward the design of novel vaccines, drugs, and diagnosis to ma- laria.展开更多
文摘Toll-like receptors(TLRs) are a central component of innate immune system and play a major role as the initiator of the innate immune responses to defend against bacteria,viruses,parasite and other pathogens.During malaria infection,TLRs signaling pathways are initialed with the recognition of Plasmodium glycosylphosphatidylinositols(GPI) and hemozoin as pathogen-associated molecular patterns(PAMPs).And then,activation of TLRs signaling induces specific biological responses against malaria parasites invasion.However,TLRs are also involved in malaria pathogenesis and enhancement of immune tolerance and evasion for malaria infection.Moreover,malaria parasites regulate selectively TLRs expression on immune cells.Thus,these evidences indicated that TLRs have contrary roles on malaria infection.Understanding the complicated roles of TLRs on malaria infection will contribute us to design more effective anti-malaria drugs or vaccines.
文摘We have previously demonstrated the ability of malaria parasites to interfere with specific immune responses. CD4 T cells specific to parasite antigens, but not CD4 T cells specific to an irrelevant antigen, ovalbumin (OVA), are de- leted via apoptosis during malaria infection. It is of interest, therefore, to investigate the immune responses that developed following vaccination with the 19 kDa carboxylterminus of the merozoite surface protein 1 (MSP119) in mice that had previ- ously experienced malaria infection. In this study, pre-exposure of mice to Plasmodium yoelii elicited native anti-MSP119 an- tibody responses, which could be boosted by vaccination with recombinant MSP119 . likewise, infection of MSP119-primed mice with Plasmodium yoelii ( P . yoelii) led to an increase of anti-MSP119 antibodies. MSP119 vaccination of malaria pre- exposed mice or immunization by infection/cure of MSP119-primed mice enabled the mice to survive challenge infection, with the former group having slightly lower parasitaemia. The data suggest that exposure to malaria infection primes a natural im- mune response which can be boosted by vaccination. This information is relevant to the development of a vaccine for use in individuals living in malaria-endemic areas.
基金supported by the National Natural Science Foundation of China(81271863,81361120405)the Key Research Program of the Chinese Academy of Sciences(KJZD-EW-L01)
文摘Both eukaryotic and prokaryotic pathogens infect the host stably via an immune evasion mecha- nism termed mutually exclusive expression. Nowadays, little is known about this epigenetic mechanism, largely limiting the understanding of pathogenesis of many bacterial, fungal and protozoan pathogens and therefore the development of novel drugs and vaccines. In the most severe malaria parasite, Plasrnodiurn falciparum, there is a major virulence gene family termed vat, by which the variant antigen PfEMP1 is encoded and expressed on the surface of parasite-infected erythrocytes. Each parasite carries about 60 anti- genically various vat genes, however, only one of which is expressed at a given time during infection. P. falciparum expresses PfEMP1s in this clonally variant manner to bind to different human endothelial re- ceptors, allowing the infected erythrocytes to sequester in tissues to escape the host＇s immune response in- cluding spleen killing and humoral immunity. At present, the mechanism of mutually exclusive expression of the var gene family remains largely unknown, even though there is increasing evidence suggesting im- portant roles of the epigenetic regulation involved in vat gene expression. In addition, epigenetic factors were also found in association with transcriptional regulation of other antigenic variant gene families in P. falciparum. In this paper, we review the current understanding of epigenetic regulations of P. falcipa- rum virulence genes with particular views toward the design of novel vaccines, drugs, and diagnosis to ma- laria.
