The effect of innate immunity on autoimmune diabetes and the expression of Toll-like receptors on pancreatic islets

J Immunol. 2004 Mar 1;172(5):3173-80. doi: 10.4049/jimmunol.172.5.3173.

Abstract

Viral infections have previously been implicated as a trigger of autoimmune diabetes. In this study, we compared a viral mimic with other microbial components derived from bacteria in triggering diabetes development in C57BL/6-rat insulin promoter-B7.1 mice that do not normally develop diabetes. It is striking that only the viral mimic induced the development of diabetes in our model system. Further mechanistic studies suggest that diabetes is induced, in part, by the combination of direct recognition of this virus-like stimulus by pancreatic islets through the expression of the innate immune receptor, Toll-like receptor 3. In addition, the functions of APCs are up-regulated, and this could stimulate islet Ag-reactive T cells that will attack beta cells leading to autoimmune diabetes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adjuvants, Immunologic / pharmacology
  • Animals
  • Apoptosis / drug effects
  • Apoptosis / immunology
  • B-Lymphocytes / immunology
  • Cells, Cultured
  • Diabetes Mellitus, Type 1 / chemically induced
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 1 / immunology*
  • Humans
  • Immunity, Innate / genetics
  • Injections, Intraperitoneal
  • Interferon-alpha / biosynthesis
  • Islets of Langerhans / immunology*
  • Islets of Langerhans / metabolism*
  • Islets of Langerhans / pathology
  • Lipopolysaccharides / administration & dosage
  • Lymphocyte Activation / drug effects
  • Membrane Glycoproteins / biosynthesis*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Inbred NOD
  • Mice, Transgenic
  • Peptidoglycan / administration & dosage
  • Poly I-C / administration & dosage
  • Poly I-C / pharmacology
  • RNA, Double-Stranded / administration & dosage
  • RNA, Viral / administration & dosage
  • Receptors, Cell Surface / biosynthesis*
  • T-Lymphocytes / immunology
  • Toll-Like Receptor 3
  • Toll-Like Receptors

Substances

  • Adjuvants, Immunologic
  • Interferon-alpha
  • Lipopolysaccharides
  • Membrane Glycoproteins
  • Peptidoglycan
  • RNA, Double-Stranded
  • RNA, Viral
  • Receptors, Cell Surface
  • TLR3 protein, human
  • Toll-Like Receptor 3
  • Toll-Like Receptors
  • Poly I-C