Probiotic Bifidobacterium breve induces IL-10-producing Tr1 cells in the colon

PLoS Pathog. 2012;8(5):e1002714. doi: 10.1371/journal.ppat.1002714. Epub 2012 May 31.

Abstract

Specific intestinal microbiota has been shown to induce Foxp3(+) regulatory T cell development. However, it remains unclear how development of another regulatory T cell subset, Tr1 cells, is regulated in the intestine. Here, we analyzed the role of two probiotic strains of intestinal bacteria, Lactobacillus casei and Bifidobacterium breve in T cell development in the intestine. B. breve, but not L. casei, induced development of IL-10-producing Tr1 cells that express cMaf, IL-21, and Ahr in the large intestine. Intestinal CD103(+) dendritic cells (DCs) mediated B. breve-induced development of IL-10-producing T cells. CD103(+) DCs from Il10(-/-), Tlr2(-/-), and Myd88(-/-) mice showed defective B. breve-induced Tr1 cell development. B. breve-treated CD103(+) DCs failed to induce IL-10 production from co-cultured Il27ra(-/-) T cells. B. breve treatment of Tlr2(-/-) mice did not increase IL-10-producing T cells in the colonic lamina propria. Thus, B. breve activates intestinal CD103(+) DCs to produce IL-10 and IL-27 via the TLR2/MyD88 pathway thereby inducing IL-10-producing Tr1 cells in the large intestine. Oral B. breve administration ameliorated colitis in immunocompromised mice given naïve CD4(+) T cells from wild-type mice, but not Il10(-/-) mice. These findings demonstrate that B. breve prevents intestinal inflammation through the induction of intestinal IL-10-producing Tr1 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Bifidobacteriales Infections / immunology
  • Bifidobacteriales Infections / microbiology
  • Bifidobacteriales Infections / therapy
  • Bifidobacterium / immunology*
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / transplantation
  • Cell Differentiation
  • Coculture Techniques
  • Colitis / immunology
  • Colitis / microbiology
  • Colitis / therapy
  • Colon / immunology
  • Colon / microbiology*
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Host-Pathogen Interactions
  • Immunocompromised Host
  • Interleukin-10 / immunology
  • Interleukin-10 / metabolism*
  • Lactobacillus casei / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Probiotics / administration & dosage*
  • T-Lymphocytes, Regulatory / cytology*
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism

Substances

  • IL10 protein, human
  • Interleukin-10