Heat Shock Protein 60 in Eggs Specifically Induces Tregs and Reduces Liver Immunopathology in Mice with Schistosomiasis Japonica.
Heat Shock Protein 60 in Eggs Specifically Induces Tregs and Reduces Liver Immunopathology in Mice with Schistosomiasis Japonica.
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DOI：
10.1371/journal.pone.0139133
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Su C
中科院分区：
文献类型：
--
作者：
Zhou S;Jin X;Chen X;Zhu J;Xu Z;Wang X;Liu F;Hu W;Zhou L;Su C
寄生蠕虫需要抑制宿主免疫系统以建立慢性感染。寄生虫引起的免疫抑制也有益于宿主，限制过度炎症和组织损伤，这仍然是导致严重发病率和死亡率的主要原因。调节性T细胞（TCFs）是这种互惠关系的关键免疫调节因子。在病毒感染过程中，T细胞的连续升高在免疫调节中起着关键作用。我们和其他人以前曾证明日本血吸虫（S.日本血吸虫卵抗原（SEA）在体内外均能诱导T细胞增殖。此外，我们还鉴定了来源于SEA的SjHSP 60在体内和体外均能显著诱导TcB。然而，SEA中SjHSP 60对Treg诱导的贡献以及Treg诱导的相关机制尚未确定。在这项研究中，我们表明，S。日本血吸虫应激蛋白HSP 60（SjHSP 60）在日本血吸虫卵中组成型广泛表达。山茱萸SjHSP 60在体内和体外特异性诱导T细胞亚群增殖，而不诱导其它CD 4 + T细胞亚群，包括Th 1、Th 2和Th 17细胞。此外，我们表明，SjHSP 60耗尽SEA几乎失去了在体外的能力，并显示出显着受损的能力，在体内诱导T细胞。最后，我们的研究表明，SjHSP 60介导的诱导TcB的机制是通过CD 4 + CD 25- T细胞转化为CD 4 + CD 25 + Foxp 3 + TcB和以TLR 4依赖的方式扩增预先存在的CD 4 + CD 25 + Foxp 3 + TcB。总的来说，我们的研究结果确定SjHSP 60是S.日本血吸虫虫卵抗原的研究不仅有助于更好地理解蠕虫感染过程中的免疫调节机制，而且表明其作为控制免疫病理学、变应性和自身免疫性疾病的治疗靶点的潜力。
Parasitic helminths need to suppress the host immune system to establish chronic infections. Paradoxically, immunosuppression induced by the worm also benefits the host by limiting excessive inflammation and tissue damage, which remains the major cause leading to serious morbidity and mortality. Regulatory T cells (Tregs) are key immune regulators of this mutualism. The successive rise in Tregs during schistosome infection plays a critical role in immunoregulation. We and others previously showed that Schistosoma japonicum (S. japonicum) egg antigens (SEA) induce Tregs both in vitro and in vivo. In addition, we identified that SjHSP60 derived from SEA significantly induces Tregs in vivo and in vitro. However, the contribution of SjHSP60 in SEA to Treg induction and the related mechanisms of the Treg induction have not yet been identified. In this study, we showed that S. japonicum stress protein HSP60 (SjHSP60) was constitutively and extensively expressed in eggs of S. japonicum. SjHSP60 specially induced Tregs in vivo and in vitro without inducing other CD4+ T sub-populations including Th1, Th2 and Th17 cells. Furthermore, we showed that the SjHSP60-depleted SEA almost lost the ability in vitro and displayed a significant impaired ability to induce Tregs in vivo. Finally, our study illustrated that the mechanisms of SjHSP60-mediated induction of Tregs are through both conversion of CD4+CD25- T cells into CD4+CD25+Foxp3+ Tregs and expansion of preexisting CD4+CD25+Foxp3+ Tregs in a TLR4-dependent manner. Collectively, our findings identify SjHSP60 as a major parasitic contributor of Treg induction in S. japonicum egg antigens, which not only contributes to the better understanding of the mechanism of immunoregulation during helminth infection, but also suggests its potential as a therapeutic target for control of immunopathology, allergic and autoimmune diseases.