title: Helminth infection can reduce insulitis and type 1 diabetes through CD25- and IL-10-independent mechanisms.
abstract: Parasitic helminth infection has been shown to modulate pathological inflammatory responses in allergy and autoimmune disease. The aim of this study was to examine the effects of infection with a helminth parasite, Heligmosomoides polygyrus, on type 1 diabetes (T1D) in nonobese diabetic (NOD) mice and to elucidate the mechanisms involved in this protection. H. polygyrus inoculation at 5 weeks of age protected NOD mice from T1D until 40 weeks of age and also inhibited the more aggressive cyclophosphamide-induced T1D. Moreover, H. polygyrus inoculation as late as 12 weeks of age reduced the onset of T1D in NOD mice. Following H. polygyrus inoculation of NOD mice, pancreatic insulitis was markedly inhibited. Interleukin-4 (IL-4), IL-10, and IL-13 expression and the frequency of CD4(+) CD25(+) FoxP3(+) regulatory T cells were elevated in mesenteric and pancreatic lymph nodes. Depletion of CD4(+) CD25(+) T cells in vivo did not abrogate H. polygyrus-induced T1D protection, nor did anti-IL-10 receptor blocking antibody. These findings suggest that infection with H. polygyrus significantly inhibits T1D in NOD mice through CD25- and IL-10-independent mechanisms and also reduces the severity of T1D when administered late after the onset of insulitis.
authors.affiliation: Department of Medicine, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, 185 S Orange Avenue, Newark, New Jersey 07103, USA.
authors.forename: Qian
authors.initials: Q
authors.lastname: Liu
authors.forename: Krishnan
authors.initials: K
authors.lastname: Sundar
authors.forename: Pankaj K
authors.initials: PK
authors.lastname: Mishra
authors.forename: Gity
authors.initials: G
authors.lastname: Mousavi
authors.forename: Zhugong
authors.initials: Z
authors.lastname: Liu
authors.forename: Andrew
authors.initials: A
authors.lastname: Gaydo
authors.forename: Farhang
authors.initials: F
authors.lastname: Alem
authors.forename: David
authors.initials: D
authors.lastname: Lagunoff
authors.forename: David
authors.initials: D
authors.lastname: Bleich
authors.forename: William C
authors.initials: WC
authors.lastname: Gause
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003922:Diabetes Mellitus, Type 1 / Q000469:parasitology* / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D016753:Interleukin-10 / Q000276:immunology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D009351:Nematospiroides dubius / Q000276:immunology*; D010179:Pancreas / Q000473:pathology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D001786:Blood Glucose; C508018:Il2ra protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D016753:Interleukin-10