Naturally transmitted segmented filamentous bacteria segregate with diabetes protection in nonobese diabetic mice

Martin A. Kriegel, Esen Sefik, Jonathan A. Hill, Hsin Jung Wu, Christophe Benoist, Diane Mathis

Research output: Contribution to journalArticle

271 Scopus citations

Abstract

Vertebrates typically harbor a rich gastrointestinal microbiota, which has coevolved with the host over millennia and is essential for several host physiological functions, in particular maturation of the immune system. Recent studies have highlighted the importance of a single bacterial species, segmented filamentous bacteria (SFB), in inducing a robust T-helper cell type 17 (Th17) population in the small-intestinal lamina propria (SI-LP) of the mouse gut. Consequently, SFB can promote IL-17-dependent immune and autoimmune responses, gut-associated as well as systemic, including inflammatory arthritis and experimental autoimmune encephalomyelitis. Here, we exploit the incomplete penetrance of SFB colonization of NOD mice in our animal facility to explore its impact on the incidence and course of type 1 diabetes in this prototypical, spontaneous model. There was a strong cosegregation of SFB positivity and diabetes protection in females, but not in males, which remained relatively disease-free regardless of the SFB status. In contrast, insulitis did not depend on SFB colonization. SFB-positive, but not SFB-negative, females had a substantial population of Th17 cells in the SI-LP, which was the only significant, repeatable difference in the examined T-cell compartments of the gut, pancreas, or systemic lymphoid tissues. Th17-signature transcripts dominated the very limited SFB-induced molecular changes detected in SI-LP CD4 + T cells. Thus, a single bacterium, and the gut immune system alterations associated with it, can either promote or protect from autoimmunity in predisposed mouse models, probably reflecting their variable dependence on different Th subsets.

Original languageEnglish (US)
Pages (from-to)11548-11553
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number28
DOIs
StatePublished - Jul 12 2011

    Fingerprint

Keywords

  • Autoimmune disease
  • Gender
  • Microbiome
  • T lymphocyte

ASJC Scopus subject areas

  • General

Cite this