Cyclophilin A from Schistosoma japonicum promotes a Th2 response in mice.

Cyclophilin A from Schistosoma japonicum promotes a Th2 response in mice.
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日本血吸虫中的亲环蛋白 A 可促进小鼠的 Th2 反应。

DOI:
10.1186/1756-3305-6-330
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发表时间:
2013-11-17
影响因子:
3.2
通讯作者:
Chen XP
Chen XP
中科院分区:
医学2区
文献类型:
--
作者:
Li J;Zhuang W;Cong L;Shi W;Cai X;Huang F;Liao Y;Liu Y;Li J;Chen C;Chen XP

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血吸虫病是一种慢性感染,当寄生虫进入卵期时,宿主对寄生虫的免疫应答从主要的Th 1表型转变为Th 2表型,抑制宿主的炎症免疫应答以实现在宿主中更长的存活。另一方面,Th 2应答的发展引起免疫病理学变化,如肝纤维化。因此,鉴定血吸虫Th 2诱导分子对了解血吸虫病的发病机制具有重要意义。日本血吸虫亲环素A同源物是日本血吸虫卵期特异性抗原,但其免疫原性和免疫调节活性尚不清楚。本研究克隆并表达了日本血吸虫亲环素A基因(SjCyP 18)。在不同发育阶段的表达谱。用RT-PCR和免疫荧光法检测了日本血吸虫的致病性。SjCyP 18的免疫原性通过在来自S.用免疫球蛋白亚类和T细胞IL-4诱导法检测SjCyP 18对Th 2细胞的促进作用。克隆的SjCyP 18与人或小鼠亲环素A在氨基酸水平上具有65%的同源性。与作为卵期特异性抗原的报道相反,发现该基因在S.山茱萸在部分血吸虫中发现了抗SjCyP 18的IgG应答。日本血吸虫感染病人,并显着诱导感染时,成为专利和感染小鼠产卵。此外,IgG 1的Th 2促进亚类是S.日本血吸虫感染小鼠。更重要的是,与PBS注射对照相比,足垫注射SjCyP 18诱导淋巴细胞产生比IFN-γ更多的IL-4。在S.日本血吸虫是免疫原性的,并在体内促进Th 2应答,这可能有助于建立慢性感染的病原体。
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. 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. 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-γ by lymphocytes compared to responses from PBS injection controls. 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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