title: Chronic helminth infection and helminth-derived egg antigens promote adipose tissue M2 macrophages and improve insulin sensitivity in obese mice.
abstract: 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.
authors: 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.
authors: Leonie
authors: L
authors: Hussaarts
authors: 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.
authors: Noemí
authors: N
authors: García-Tardón
authors: 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.
authors: Lianne
authors: L
authors: van Beek
authors: 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.
authors: Mattijs M
authors: MM
authors: Heemskerk
authors: 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.
authors: Simone
authors: S
authors: Haeberlein
authors: 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.
authors: Gerard C
authors: GC
authors: van der Zon
authors: 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.
authors: Arifa
authors: A
authors: Ozir-Fazalalikhan
authors: 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.
authors: Jimmy F P
authors: JF
authors: Berbée
authors: 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.
authors: Ko
authors: K
authors: Willems van Dijk
authors: 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.
authors: Vanessa
authors: V
authors: van Harmelen
authors: 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.
authors: Maria
authors: M
authors: Yazdanbakhsh
authors: 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 b.g.a.guigas@lumc.nl.
authors: Bruno
authors: B
authors: Guigas
mesh_terms: D052436:Adipose Tissue, White / Q000276:immunology / Q000473:pathology; D000818:Animals; D000947:Antigens, Helminth / Q000008:administration & dosage*; D002908:Chronic Disease; D059305:Diet, High-Fat / Q000009:adverse effects; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007333:Insulin Resistance / Q000276:immunology* / Q000502:physiology; D008099:Liver / Q000276:immunology; D008262:Macrophage Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000150:complications* / Q000276:immunology* / Q000378:metabolism; D012550:Schistosoma mansoni / Q000276:immunology; D012555:Schistosomiasis mansoni / Q000150:complications* / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology
chemical_list: D000947:Antigens, Helminth
keywords: Schistosoma mansoni; eosinophils; immunometabolism; type 2 inflammation