Secreted proteins from the helminth Fasciola hepatica inhibit the initiation of autoreactive T cell responses and prevent diabetes in the NOD mouse.
Secreted proteins from the helminth Fasciola hepatica inhibit the initiation of autoreactive T cell responses and prevent diabetes in the NOD mouse.
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来自蠕虫筋膜的分泌蛋白抑制自动反应性T细胞反应的启动，并防止NOD小鼠中的糖尿病。
DOI：
10.1371/journal.pone.0086289
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Donnelly S
中科院分区：
文献类型：
--
作者：
Lund ME;O'Brien BA;Hutchinson AT;Robinson MW;Simpson AM;Dalton JP;Donnelly S
感染寄生虫可预防/减轻自身炎症性疾病。在这里，我们发现由寄生虫分泌的分子可以预防非肥胖糖尿病（NOD）小鼠的1型糖尿病（T1D）。当在4周龄分娩时（与自身免疫的开始一致），肝片形吸虫（FhES）的排泄/分泌产物阻止了T1D的发生，84%的小鼠在30周龄时保持血糖正常和无胰岛素。疾病保护与抑制自身反应性T细胞的IFN-γ分泌和转换到自身抗体的调节同型（从IgG2a到IgG1）的产生有关。注射FhES后，腹腔巨噬细胞转化为调节性M2表型，其特征是Ym1、Arg-1、TGFβ和PD-L1的表达水平增加。这些M2遗传标记在fhes处理小鼠的胰腺淋巴结和胰腺中的表达增加。在体外，fhes刺激的M2巨噬细胞诱导naïve NOD小鼠脾细胞向Tregs分化。总的来说，我们的数据表明FhES含有免疫调节分子，通过诱导和维持调节免疫环境来介导对自身免疫性糖尿病的保护。
Infections with helminth parasites prevent/attenuate auto-inflammatory disease. Here we show that molecules secreted by a helminth parasite could prevent Type 1 Diabetes (T1D) in nonobese diabetic (NOD) mice. When delivered at 4 weeks of age (coincident with the initiation of autoimmunity), the excretory/secretory products of Fasciola hepatica (FhES) prevented the onset of T1D, with 84% of mice remaining normoglycaemic and insulitis-free at 30 weeks of age. Disease protection was associated with suppression of IFN-γ secretion from autoreactive T cells and a switch to the production of a regulatory isotype (from IgG2a to IgG1) of autoantibody. Following FhES injection, peritoneal macrophages converted to a regulatory M2 phenotype, characterised by increased expression levels of Ym1, Arg-1, TGFβ and PD-L1. Expression of these M2 genetic markers increased in the pancreatic lymph nodes and the pancreas of FhES-treated mice. In vitro, FhES-stimulated M2 macrophages induced the differentiation of Tregs from splenocytes isolated from naïve NOD mice. Collectively, our data shows that FhES contains immune-modulatory molecules that mediate protection from autoimmune diabetes via the induction and maintenance of a regulatory immune environment.
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