title: Filarial Infection or Antigen Administration Improves Glucose Tolerance in Diet-Induced Obese Mice.
abstract: 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 Lpl). 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.
authors.affiliation: Institute for Medical Microbiology, Immunology and Parasitology, University Hospital of Bonn, Bonn, Germany.
authors.forename: Afiat
authors.initials: A
authors.lastname: Berbudi
authors.forename: Jayagopi
authors.initials: J
authors.lastname: Surendar
authors.forename: Jesuthas
authors.initials: J
authors.lastname: Ajendra
authors.forename: Fabian
authors.initials: F
authors.lastname: Gondorf
authors.forename: David
authors.initials: D
authors.lastname: Schmidt
authors.forename: Anna-Lena
authors.initials: AL
authors.lastname: Neumann
authors.forename: Ajeng P F
authors.initials: AP
authors.lastname: Wardani
authors.forename: Laura E
authors.initials: LE
authors.lastname: Layland
authors.forename: Linda S
authors.initials: LS
authors.lastname: Hoffmann
authors.forename: Alexander
authors.initials: A
authors.lastname: Pfeifer
authors.forename: Achim
authors.initials: A
authors.lastname: Hoerauf
authors.forename: Marc P
authors.initials: MP
authors.lastname: Hübner
mesh_terms: D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology*; D004032:Diet; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology*; D005368:Filariasis / Q000276:immunology*; D005370:Filarioidea / Q000276:immunology*; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D050356:Lipid Metabolism / Q000235:genetics; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000276:immunology*; D015398:Signal Transduction / Q000235:genetics; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D000947:Antigens, Helminth