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

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

Author information

1
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037.
2
Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
3
Division of Gastroenterology, BC Children's Hospital, Vancouver, British Columbia, Canada State Key.
4
State Key Laboratory of Cellular Stress Biology and School of Life Sciences, Xiamen University, Xiamen, Fujian, China.
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Contributed equally

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.

PMID:
23918973
PMCID:
PMC3770349
DOI:
10.4049/jimmunol.1300908
[Indexed for MEDLINE]
Free PMC Article

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