Prevention of type 1 diabetes through infection with an intestinal nematode parasite requires IL-10 in the absence of a Th2-type response.
Helminth infection can prevent type 1 diabetes (T1D); however, the regulatory mechanisms inhibiting disease remain largely undefined. In these studies, nonobese diabetic (NOD) IL-4(-/-) mice were infected with the strictly enteric nematode parasite, Heligmosomoides polygyrus. Short-term infection, 5-7 weeks of age, inhibited T1D onset, as late as 40 weeks of age. CD4(+) T-cell STAT6 phosphorylation was inhibited, while suppressed signal transducer and activator of transcription 1 phosphorylation was sustained, as were increases in FOXP3(-), CD4(+) T-cell interleukin (IL)-10 production. Blockade of IL-10 signaling in NOD-IL-4(-/-), but not in NOD, mice during this short interval abrogated protective effects resulting in pancreatic β-cell destruction and ultimately T1D. Transfer of CD4(+) T cells from H. polygyrus (Hp)-inoculated NOD IL-4(-/-) mice to NOD mice blocked the onset of T1D. These studies indicate that Hp infection induces non-T-regulatory cells to produce IL-10 independently of STAT6 signaling and that in this Th2-deficient environment IL-10 is essential for T1D inhibition.
Center for Immunity and Inflammation, Department of Medicine, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey, USA.
P K
PK
Mishra
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N
Patel
W
W
Wu
D
D
Bleich
W C
WC
Gause
D000818:Animals; D001324:Autoantigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000517:prevention & control*; D005260:Female; D005786:Gene Expression Regulation; D050417:Insulin-Secreting Cells / Q000473:pathology; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000276:immunology* / Q000378:metabolism; D015847:Interleukin-4 / Q000172:deficiency; D007422:Intestines / Q000469:parasitology*; D007515:Islets of Langerhans / Q000276:immunology; D008221:Lymphoid Tissue / Q000276:immunology / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D009351:Nematospiroides dubius / Q000276:immunology*; D010641:Phenotype; D010766:Phosphorylation; D053701:Receptors, Interleukin-10 / Q000037:antagonists & inhibitors; D050794:STAT1 Transcription Factor / Q000378:metabolism; D050800:STAT6 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D017206:Strongylida Infections / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism
D001324:Autoantigens; D016207:Cytokines; D053701:Receptors, Interleukin-10; D050794:STAT1 Transcription Factor; D050800:STAT6 Transcription Factor; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma