Hussaarts Leonie, García-Tardón Noemí, van Beek Lianne, Heemskerk Mattijs M, Haeberlein Simone, van der Zon Gerard C, Ozir-Fazalalikhan Arifa, Berbée Jimmy F P, Willems van Dijk Ko, van Harmelen Vanessa, Yazdanbakhsh Maria, Guigas Bruno
Departments of *Parasitology, Human Genetics, Molecular Cell Biology, and Endocrinology and Metabolic Diseases, Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands.
Departments of *Parasitology, Human Genetics, Molecular Cell Biology, and Endocrinology and Metabolic Diseases, Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands
FASEB J. 2015 Jul;29(7):3027-39. doi: 10.1096/fj.14-266239. Epub 2015 Apr 7.
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 obese mice. 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 obese C57BL/6 male 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%) and WAT insulin 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 in WAT 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.
与肥胖相关的慢性低度炎症会导致胰岛素抵抗和2型糖尿病。蠕虫寄生虫是2型免疫反应最强的天然诱导剂,据报道,啮齿动物线虫的短期感染可改善肥胖小鼠的葡萄糖耐量。在此,我们研究了曼氏血吸虫(一种感染全球数百万人的蠕虫)对高脂饮食诱导的肥胖C57BL/6雄性小鼠全身代谢稳态和白色脂肪组织(WAT)免疫细胞组成的慢性感染(12周)影响。我们的数据表明,慢性蠕虫感染减少了体重增加(-62%)、脂肪量增加(-89%)和脂肪细胞大小;降低了全身胰岛素抵抗(-23%)和葡萄糖不耐受(-16%);并改善了外周葡萄糖摄取(+25%)和WAT胰岛素敏感性。通过流式细胞术和定量PCR(qPCR)分析免疫细胞组成发现,曼氏血吸虫促进了WAT嗜酸性粒细胞和交替激活(M2)巨噬细胞的大量增加。重要的是,注射曼氏血吸虫可溶性虫卵抗原(SEA)重现了寄生虫感染对全身代谢稳态的有益作用,并在WAT和肝脏中诱导了2型免疫反应。综上所述,我们提供了新的数据,表明慢性蠕虫感染和蠕虫衍生分子通过促进辅助性T细胞2(Th2)反应、嗜酸性粒细胞增多和WAT M2极化来预防代谢紊乱。
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