MicroRNA-155 is essential for the T cell-mediated control of Helicobacter pylori infection and for the induction of chronic Gastritis and Colitis

J Immunol. 2011 Oct 1;187(7):3578-86. doi: 10.4049/jimmunol.1101772. Epub 2011 Aug 31.

Abstract

MicroRNAs govern immune responses to infectious agents, allergens, and autoantigens and function by posttranscriptional repression of their target genes. In this paper, we have addressed the role of microRNA-155 (miR-155) in the control of Helicobacter pylori infection of the gastrointestinal tract and the development of H. pylori-induced chronic gastritis and associated gastric preneoplastic pathology. We show that miR-155 is upregulated in the gastric mucosa of experimentally infected mice and that miR-155(-/-) mice fail to control H. pylori infection as a result of impaired pathogen-specific Th1 and Th17 responses. miR-155(-/-) mice are also less well protected against challenge infection after H. pylori-specific vaccination than their wild-type (wt) counterparts. As a consequence of their impaired T cell responses to H. pylori, miR-155(-/-) mice develop less severe infection-induced immunopathology manifesting as chronic atrophic gastritis, epithelial hyperplasia, and intestinal metaplasia. T cells from miR-155(-/-) mice that are activated by CD3/CD28 cross-linking expand less and produce less IFN-γ and IL-17 than wt T cells. Finally, we show in this paper using adoptive transfers that the phenotypes of miR-155(-/-) mice are likely due to T cell-intrinsic defects. In contrast to wt T cells, miR-155(-/-) T cells from infected donors do not control H. pylori infections in T cell-deficient recipients, do not differentiate into Th1 or Th17 cells, and do not cause immunopathology. In addition, naive miR-155(-/-) T cells fail to induce chronic Th17-driven colitis in an adoptive transfer model. In conclusion, miR-155 expression is required for the Th17/Th1 differentiation that underlies immunity to H. pylori infection on the one hand and infection-associated immunopathology on the other.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Cell Differentiation / immunology
  • Cell Separation
  • Chronic Disease
  • Colitis / genetics*
  • Colitis / immunology
  • Colitis / microbiology
  • Flow Cytometry
  • Gastric Mucosa / immunology
  • Gastric Mucosa / microbiology
  • Gastritis / genetics*
  • Gastritis / immunology
  • Gastritis / microbiology
  • Helicobacter Infections / genetics*
  • Helicobacter Infections / immunology
  • Helicobacter pylori / immunology*
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • MicroRNAs / immunology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*

Substances

  • MicroRNAs
  • Mirn155 microRNA, mouse