Activation of p38α in T cells regulates the intestinal host defense against attaching and effacing bacterial infections

J Immunol. 2013 Sep 1;191(5):2764-2770. doi: 10.4049/jimmunol.1300908. Epub 2013 Aug 5.

Abstract

Intestinal infections by attaching and effacing (A/E) bacterial pathogens cause severe colitis and bloody diarrhea. Although p38α in intestinal epithelial cells (IEC) plays an important role in promoting protection against A/E bacteria by regulating T cell recruitment, its impact on immune responses remains unclear. In this study, we show that activation of p38α in T cells is critical for the clearance of the A/E pathogen Citrobacter rodentium. Mice deficient of p38α in T cells, but not in macrophages or dendritic cells, were impaired in clearing C. rodentium. Expression of inflammatory cytokines such as IFN-γ by p38α-deficient T cells was reduced, which further reduced the expression of inflammatory cytokines, chemokines, and antimicrobial peptide by IECs and led to reduced infiltration of T cells into the infected colon. Administration of IFN-γ activated the mucosal immunity to C. rodentium infection by increasing the expression of inflammation genes and the recruitment of T cells to the site of infection. Thus, p38α contributes to host defense against A/E pathogen infection by regulating the expression of inflammatory cytokines that activate host defense pathways in IECs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Citrobacter rodentium
  • Dendritic Cells / enzymology
  • Dendritic Cells / immunology
  • Disease Models, Animal
  • Enterobacteriaceae Infections / enzymology*
  • Enterobacteriaceae Infections / immunology
  • Enzyme Activation / immunology*
  • Epithelial Cells / immunology
  • Epithelial Cells / metabolism
  • Flow Cytometry
  • Gastroenteritis / enzymology
  • Gastroenteritis / immunology
  • Immunity, Mucosal / immunology*
  • Immunohistochemistry
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / metabolism
  • Lymphocyte Activation / immunology
  • Macrophages / enzymology
  • Macrophages / immunology
  • Mice
  • Mice, Transgenic
  • Mitogen-Activated Protein Kinase 14 / metabolism*
  • Real-Time Polymerase Chain Reaction
  • T-Lymphocytes / enzymology*
  • T-Lymphocytes / immunology

Substances

  • Mitogen-Activated Protein Kinase 14