Prevention of type 1 diabetes through infection with an intestinal nematode parasite requires IL-10 in the absence of a Th2-type response

Mucosal Immunol. 2013 Mar;6(2):297-308. doi: 10.1038/mi.2012.71. Epub 2012 Jul 18.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoantigens / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • Cytokines / genetics
  • Cytokines / immunology
  • Diabetes Mellitus, Type 1 / immunology*
  • Diabetes Mellitus, Type 1 / prevention & control*
  • Female
  • Gene Expression Regulation
  • Insulin-Secreting Cells / pathology
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism
  • Interleukin-10 / immunology*
  • Interleukin-10 / metabolism
  • Interleukin-4 / deficiency
  • Intestines / parasitology*
  • Islets of Langerhans / immunology
  • Lymphoid Tissue / immunology
  • Lymphoid Tissue / metabolism
  • Mice
  • Mice, Inbred NOD
  • Mice, Knockout
  • Nematospiroides dubius / immunology*
  • Phenotype
  • Phosphorylation
  • Receptors, Interleukin-10 / antagonists & inhibitors
  • STAT1 Transcription Factor / metabolism
  • STAT6 Transcription Factor / metabolism
  • Signal Transduction
  • Strongylida Infections / immunology*
  • Th1 Cells / immunology
  • Th1 Cells / metabolism
  • Th2 Cells / immunology*
  • Th2 Cells / metabolism

Substances

  • Autoantigens
  • Cytokines
  • Receptors, Interleukin-10
  • STAT1 Transcription Factor
  • STAT6 Transcription Factor
  • Interleukin-10
  • Interleukin-4
  • Interferon-gamma