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Tim-3 induces Th2-biased immunity and alternative macrophage activation during Schistosoma japonicum infection.

ABSTRACT: T cell immunoglobulin- and mucin-domain-containing molecule 3 (Tim-3) has been regarded as an important regulatory factor in both adaptive and innate immunity. Recently, Tim-3 was reported to be involved in Th2-biased immune responses in mice infected with Schistosoma japonicum, but the exact mechanism behind the involvement of Tim-3 remains unknown. The present study aims to understand the role of Tim-3 in the immune response against S. japonicum infection. Tim-3 expression was determined by flow cytometry, and increased Tim-3 expression was observed on CD4(+) and CD8(+) T cells, NK1.1(+) cells, and CD11b(+) cells from the livers of S. japonicum-infected mice. However, the increased level of Tim-3 was lower in the spleen than in the liver, and no increase in Tim-3 expression was observed on splenic CD8(+) T cells or CD11b(+) cells. The schistosome-induced upregulation of Tim-3 on natural killer (NK) cells was accompanied by reduced NK cell numbers in vitro and in vivo. Tim-3 antibody blockade led to upregulation of inducible nitric oxide synthase and interleukin-12 (IL-12) mRNA in CD11b(+) cells cocultured with soluble egg antigen and downregulation of Arg1 and IL-10, which are markers of M2 macrophages. In summary, we observed schistosome-induced expression of Tim-3 on critical immune cell populations, which may be involved in the Th2-biased immune response and alternative activation of macrophages during infection.

SUBMITTER: Hou N

PROVIDER: S-EPMC4496598 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Tim-3 induces Th2-biased immunity and alternative macrophage activation during Schistosoma japonicum infection.

Hou Nan N Piao Xianyu X Liu Shuai S Wu Chuang C Chen Qijun Q

Infection and immunity 20150518 8

T cell immunoglobulin- and mucin-domain-containing molecule 3 (Tim-3) has been regarded as an important regulatory factor in both adaptive and innate immunity. Recently, Tim-3 was reported to be involved in Th2-biased immune responses in mice infected with Schistosoma japonicum, but the exact mechanism behind the involvement of Tim-3 remains unknown. The present study aims to understand the role of Tim-3 in the immune response against S. japonicum infection. Tim-3 expression was determined by fl ...[more]

PMID: 25987707

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Project description:BACKGROUND: Schistosomiasis is a chronic infection, where the host immune response to the parasite changes from a predominantly Th1 to Th2 phenotype, when parasite enters the egg stage, restraining the host inflammatory immune responses to achieve a longer survival in the host. On the other hand, the development of Th2 responses causes immunopathological changes such as liver fibrosis. Therefore identification of schistosome-derived Th2 inducing molecules is important in the understanding of pathogenesis of schistosomiasis. A cyclophilin A homologue of Schistosoma japonicum was reported to be an egg-stage specific antigen, but its immunogenicity and immunoregulatory activities remain unknown. METHODS: We cloned and expressed the gene of cyclophilin A from Schistosoma japonicum (AY814078), named as SjCyP18 based on its molecular weight. The expression profiles in different stages of S. japonicum were examined by RT-PCR and immunofluorescence assay. The immunogenicity of SjCyP18 was measured by the presence of IgG in the sera from S. japonicum infected patients and animals, and the Th2-promting activities were examined by the subclass of immunoglobulins against SjCyP18 and by the IL-4 induction in T cells following footpad injection of SjCyP18. RESULTS: The cloned SjCyP18 has 65% homology with human or mouse cyclophilin A at the amino acid level. In contrast to reports as an egg-stage specific antigen, the gene was found to be expressed in all stages of S. japonicum. IgG responses against SjCyP18 were found in some S. japonicum infected patients and were significantly induced when infection become patent and produce eggs in infected mice. Furthermore, the Th2-promoting subclass of IgG1 was the predominant isotype in S. japonicum infected mice. More importantly, footpad injection of SjCyP18 induced a greater production of IL-4 than that of IFN-? by lymphocytes compared to responses from PBS injection controls. CONCLUSION: The cyclophilin A homologue found in S. japonicum is immunogenic and promotes Th2 responses in vivo which may contribute to the establishment of chronic infection by schistosomes.

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Tim-3 induces Th2-biased immunity and alternative macrophage activation during Schistosoma japonicum infection.

Publications

Tim-3 induces Th2-biased immunity and alternative macrophage activation during Schistosoma japonicum infection.

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