Induction and regulation of Protective immune responses against malaria parasites

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1.Modulation of T-cell immune responses by malaria parasitesWe studied immune responses and the protective effect of CD4^+ T-cells in mice recovered from P.yoelii 17XNL infection. CD4^+ T-cells from spleen of mice recovered from malaria infection showed spesific proliferative responses. However, they produced limited levels of IL-2 and high levels of IL-10. Adoptive transfer of these purified CD4^+ T-cells could not confer protective immunity against sporozoite infection. These results suggested that CD4^+ T-cells in Plasmodium-infected mice are functionally modulated.2.Function of dendritic cells in malaria-infected miceWe characterized function of dendritic cells from mice infected with P.yoelii. Production of IL-12 in response to Toll-like receptor stimulation was reduced when compared with normal dendritic cells while IL-10 production was augmented. The ability to activate antigen specific T-cells was not reduced in both MHC class I and class II pathways. We will continue to study molecular mechanisms underlying augmented IL-10 production and function of T-cells activated by these dendritic cells.3.Function of IRF-4, transcription factor that regulates immune responses, in dendritic cells and macrophagesTranscription factor IRF-4 is expressed in immune cells including lymphocytes, dendritic cells and macrophages. We have revealed that IRF-4 plays a critical role for the differentiation of a subset of dendritic cells and has inhibitory role for the TLR-mediated signaling. This inhibition mainly regulates activation of MAP kinase JNK and NF-κB.