Filarial Infection or Antigen Administration Improves Glucose Tolerance in Diet-Induced Obese Mice
Filarial Infection or Antigen Administration Improves Glucose Tolerance in Diet-Induced Obese Mice
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DOI：
10.1159/000448401
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发表时间：
2016-01-01
影响因子：
5.3
通讯作者：
Huebner, Marc P.
中科院分区：
文献类型：
--
作者：
Berbudi, Afiat;Surendar, Jayagopi;Huebner, Marc P.
蠕虫诱导2型免疫应答，并在其宿主中建立抗炎环境。这种免疫调节以前被证明可以改善与慢性炎症相关的饮食诱导的胰岛素抵抗。在目前的研究中，我们证明，感染丝虫Litomosoides sigmodontis增加嗜酸性粒细胞的数量和替代激活的巨噬细胞丰度在附睾脂肪组织（EAT）和改善葡萄糖耐量在饮食诱导的肥胖小鼠嗜酸性粒细胞依赖的方式。L.乙状结肠炎抗原（LsAg）给药既不改变动物的体重，也不改变脂肪组织质量或脂肪细胞大小，但它在EAT中触发2型免疫应答、嗜酸性粒细胞、交替激活的巨噬细胞和2型先天淋巴样细胞。即使在Foxp3+调节性T细胞不存在的情况下，LsAg治疗仍能改善葡萄糖耐量。此外，PCR阵列结果显示，LsAg治疗减少了炎症免疫反应，并增加了与胰岛素信号（Glut4，Pde3b，Pik3r1和Hk2）和脂肪酸摄取（Fabp4和Lp1）相关的基因的表达。我们的调查表明，L。乙状结肠炎感染和LsAg给药减少饮食诱导EAT炎症并改善葡萄糖耐量。因此，蠕虫衍生产品可能为改善胰岛素敏感性提供新的选择，而发展中国家和发达国家蠕虫感染的减少可能导致最近2型糖尿病患病率的增加。(C)2016 S. Karger AG，巴塞尔
Helminths induce type 2 immune responses and establish an anti-inflammatory milieu in their hosts. This immunomodulation was previously shown to improve diet-induced insulin resistance which is linked to chronic inflammation. In the current study, we demonstrate that infection with the filarial nematode Litomosoides sigmodontis increased the eosinophil number and alternatively activated macrophage abundance within epididymal adipose tissue (EAT) and improved glucose tolerance in diet-induced obese mice in an eosinophil-dependent manner. L. sigmodontis antigen (LsAg) administration neither altered the body weight of animals nor adipose tissue mass or adipocyte size, but it triggered type 2 immune responses, eosinophils, alternatively activated macrophages, and type 2 innate lymphoid cells in EAT. Improvement in glucose tolerance by LsAg treatment remained even in the absence of Foxp3+ regulatory T cells. Furthermore, PCR array results revealed that LsAg treatment reduced inflammatory immune responses and increased the expression of genes related to insulin signaling (Glut4, Pde3b, Pik3r1, and Hk2) and fatty acid uptake (Fabp4 and Lp1). Our investigation demonstrates that L. sigmodontis infection and LsAg administration reduce diet-induced EAT inflammation and improve glucose tolerance. Helminth-derived products may, therefore, offer new options to improve insulin sensitivity, while loss of helminth infections in developing and developed countries may contribute to the recent increase in the prevalence of type 2 diabetes. (C) 2016 S. Karger AG, Basel