Chronic helminth infection and helminth-derived egg antigens promote adipose tissue M2 macrophages and improve insulin sensitivity in obese mice
Chronic helminth infection and helminth-derived egg antigens promote adipose tissue M2 macrophages and improve insulin sensitivity in obese mice
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DOI：
10.1096/fj.14-266239
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发表时间：
2015-07-01
期刊：
影响因子：
4.8
通讯作者：
Guigas, Bruno
中科院分区：
文献类型：
--
作者：
Hussaarts, Leonie;Garcia-Tardon, Noemi;Guigas, Bruno
与肥胖相关的慢性低度炎症导致胰岛素抵抗和2型糖尿病。蠕虫寄生虫是2型免疫应答的最强天然诱导物，并且据报道啮齿动物线虫的短期感染可改善肥胖症患者的葡萄糖耐量。在此，我们研究了慢性感染曼氏血吸虫（一种感染全球数百万人的蠕虫）（12周）对高脂饮食诱导的肥胖C57 BL/6雄性小鼠全身代谢稳态和白色脂肪组织（WAT）免疫细胞组成的影响。我们的数据表明，慢性蠕虫感染减少体重增加（-62%），脂肪量增加（-89%）和脂肪细胞大小;降低全身胰岛素抵抗（-23%）和葡萄糖耐受不良（-16%）;改善外周葡萄糖摄取（+25%）和WAT胰岛素敏感性。流式细胞术和定量PCR（qPCR）分析免疫细胞组成表明，S。mansoni促进了WAT嗜酸性粒细胞和交替激活的（M2）巨噬细胞的强烈增加。重要的是，注射S.曼氏血吸虫可溶性虫卵抗原（SEA）在WAT和肝脏中诱导了2型免疫应答，并再现了寄生虫感染对全身代谢稳态的有益作用。两者合计，我们提供了新的数据表明，慢性蠕虫感染和蠕虫衍生的分子通过促进辅助性T细胞2（Th 2）反应，嗜酸性粒细胞增多症，WAT M2极化，防止代谢紊乱。
Chronic low-grade inflammation associated with obesity contributes to insulin resistance and type 2 diabetes. Helminth parasites are the strongest natural inducers of type 2 immune responses, and short-lived infection with rodent nematodes was reported to improve glucose tolerance in obesemice. Here, we investigated the effects of chronic infection (12 weeks) with Schistosoma mansoni, a helminth that infects millions of humans worldwide, on whole-body metabolic homeostasis and white adipose tissue (WAT) immune cell composition in high-fat diet-induced obeseC57BL/6male mice. Our data indicate that chronic helminth infection reduced body weight gain (-62%), fat mass gain (-89%), and adipocyte size; lowered whole-body insulin resistance (-23%) and glucose intolerance (-16%); and improved peripheral glucose uptake (+25%) andWATinsulin sensitivity. Analysis of immune cell composition by flow cytometry and quantitative PCR (qPCR) revealed that S. mansoni promoted strong increases in WAT eosinophils and alternatively activated (M2) macrophages. Importantly, injections with S. mansoni-soluble egg antigens (SEA) recapitulated the beneficial effect of parasite infection on whole-body metabolic homeostasis and induced type 2 immune responses inWAT and liver. Taken together, we provide novel data suggesting that chronic helminth infection and helminth-derived molecules protect against metabolic disorders by promoting a T helper 2 (Th2) response, eosinophilia, and WAT M2 polarization.