Immunity to blood-stage murine malarial parasites is MHC class II dependent

Cigel, Francine; Batchelder, Joan; Burns, James M.; Yañez, D M; Heyde, Henri van der; Manning, Dean D.; Weidanz, William P.

doi:10.1016/s0165-2478(03)00152-4

Cited by 24 publications

(15 citation statements)

References 36 publications

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“…To characterize the contribution of TLR7 signaling to early cytokine production, we assessed the levels of proinflammatory cytokines that have previously been implicated in control of malaria infection (14,(60)(61)(62)(63), as well as IL-10, which limits malaria-induced pathology (64). IL-10, TNF, IL-12, and IFN-␥ (the expression of which is dependent on IL-12 signaling [14]) were all significantly reduced in Tlr7 Ϫ/Ϫ , Unc93b1 3d/3d , and Myd88 Ϫ/Ϫ , but not Tlr9 Ϫ/Ϫ , mice 24 h after infection at both the mRNA and protein levels ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Toll-Like Receptor 7 Mediates Early Innate Immune Responses to Malaria

et al. 2013

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Innate immune recognition of malaria parasites is the critical first step in the development of the host response. At present, Tolllike receptor 9 (TLR9) is thought to play a central role in sensing malaria infection. However, we and others have observed that Tlr9 ؊/؊ mice, in contrast to mice deficient in the downstream adaptor, Myeloid differentiation primary response gene 88 (MYD88), exhibit few deficiencies in immune function during early infection with the malaria parasite Plasmodium chabaudi, implying that another MYD88-dependent receptor also contributes to the antimalarial response. Here we use candidate-based screening to identify TLR7 as a key sensor of early P. chabaudi infection. We show that TLR7 mediates a rapid systemic response to infection through induction of cytokines such as type I interferons (IFN-I), interleukin 12, and gamma interferon. TLR7 is also required for induction of IFN-I by other species and strains of Plasmodium, including an etiological agent of human disease, P. falciparum, suggesting that malaria parasites harbor a common pathogen-associated molecular pattern (PAMP) recognized by TLR7. In contrast to the nonredundant requirement for TLR7 in early immune activation, sensing through both TLR7 and TLR9 was required for proinflammatory cytokine production and immune cell activation during the peak of parasitemia. Our findings indicate that TLR7 plays a central role in early immune activation during malaria infection, whereas TLR7 and TLR9 contribute combinatorially to immune responses as infection progresses.

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Section: Resultsmentioning

confidence: 99%

Toll-Like Receptor 7 Mediates Early Innate Immune Responses to Malaria

et al. 2013

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“…yoelii- and P . chabaudi -infected RBCs (iRBCs), CD4 + αβ T cells respond to Plasmodium -iRBCs after priming with malarial antigens in an MHC class II context on DCs (40). CD4 + αβ T cells strongly increase their ability to produce IFN-γ after infection with P .…”

Section: Ifn-γ Producers and Their Activation In Plasmodium Infectionmentioning

confidence: 99%

Roles of IFN-γ and γδ T Cells in Protective Immunity Against Blood-Stage Malaria

Inoue¹,

Niikura²,

Mineo³

et al. 2013

Front. Immunol.

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Malaria is caused by infection with Plasmodium parasites. Various studies with knockout mice have indicated that IFN-γ plays essential roles in protective immunity against blood-stage Plasmodium infection. However, after Plasmodium infection, increased IFN-γ production by various types of cells is involved not only in protective immunity, but also in immunopathology. Recent reports have shown that IFN-γ acts as a pro-inflammatory cytokine to induce not only the activation of macrophages, but also the generation of uncommon myelolymphoid progenitor cells after Plasmodium infection. However, the effects of IFN-γ on hematopoietic stem cells and progenitor cells are unclear. Therefore, the regulation of hematopoiesis by IFN-γ during Plasmodium infection remains to be clarified. Although there are conflicting reports concerning the significance of γδ T cells in protective immunity against Plasmodium infection, γδ T cells may respond to infection and produce IFN-γ as innate immune cells in the early phase of blood-stage malaria. Our recent studies have shown that γδ T cells express CD40 ligand and produce IFN-γ after Plasmodium infection, resulting in the enhancement of dendritic cell activation as part of the immune response to eliminate Plasmodium parasites. These data suggest that the function of γδ T cells is similar to that of NK cells. Although several reports suggest that γδ T cells have the potential to act as memory cells for various infections, it remains to be determined whether memory γδ T cells are generated by Plasmodium infection and whether memory γδ T cells can contribute to the host defense against re-infection with Plasmodium. Here, we summarize and discuss the effects of IFN-γ and the various functions of γδ T cells in blood-stage Plasmodium infection.

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“…Many studies have painstakingly shown that CD8+ lymphocyte-mediated cytolytic activity aimed at destroying sporozoite infected hepatocytes is strain-specific [232,233] and that a CD4+ mediated immune response is also genetically restricted by MHC Class I molecules [234,235]. By the same token, an antibody-mediated immune response against sporozoite proteins comes largely under the genetic control of MHC Class II molecules [208,[236][237][238][239] and it has been shown that protective immunity against merozoites is genetically controlled by Class II molecules, mainly the HLA-DR genetic region in both humans [240,241] and the Aotus monkey experimental model [14,16,71,242].…”

Section: Immunological Support For Including These Modified Habps As mentioning

confidence: 99%

Functional, Immunological and Three-Dimensional Analysis of Chemically Synthesised Sporozoite Peptides as Components of a Fully-Effective Antimalarial Vaccine

Curtidor¹,

Vanegas

Alba

et al. 2011

CMC

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Our ongoing search for a fully-effective vaccine against the Plasmodium falciparum parasite (causing the most lethal form of human malaria) has been focused on identifying and characterising proteins' amino acid sequences (high activity binding peptides or HABPs) involved in parasite invasion of red blood cells (RBC) by the merozoite and hepatocytes by the sporozoite. Many such merozoite HABPs have been recognised and molecularly and structurally characterised; however, native HABPs are immunologically silent since they do not induce any immune response or protection against P. falciparum malaria infection and they have to be structurally modified to allow them to fit perfectly into immune system molecules. A deeply structural analysis of these conserved merozoite HABPs and their modified analogues has led to rules or principles becoming recognised for constructing a logical and rational methodology for a minimal subunit-based, multi-epitope, multi-stage, chemically-synthesised vaccine. The same in-depth analysis of the most relevant sporozoite proteins involved in sporozoite cell-traversal and hepatocyte invasion as well as the hepatic stage is shown here. Specifically modifying these HABPs has resulted in a new set of potential pre-erythrocyte targets which are able to induce high, longlasting antibody titres in Aotus monkeys, against their corresponding recombinant proteins and the complete parasite native molecules. This review shows how these rules may be applied against the first stage of parasite invasion (i.e. the sporozoite) to mount the first line of defence against the malarial parasite, which may indeed be the most effective one. Our results strongly support including some of these modified sporozoite HABPs in combination with the previously-described modified merozoite HABPs for obtaining the aforementioned fully-protective, multiepitope, multi-stage, minimal subunit-based, chemically-synthesized, antimalarial vaccine.

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Immunity to blood-stage murine malarial parasites is MHC class II dependent

Cited by 24 publications

References 36 publications

Toll-Like Receptor 7 Mediates Early Innate Immune Responses to Malaria

Toll-Like Receptor 7 Mediates Early Innate Immune Responses to Malaria

Roles of IFN-γ and γδ T Cells in Protective Immunity Against Blood-Stage Malaria

Functional, Immunological and Three-Dimensional Analysis of Chemically Synthesised Sporozoite Peptides as Components of a Fully-Effective Antimalarial Vaccine

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