title: Activation of p38α in T cells regulates the intestinal host defense against attaching and effacing bacterial infections.
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.
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037.
authors.forename: Eun-Jin
authors.initials: EJ
authors.lastname: Shim
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037.
authors.forename: Bo Ram
authors.initials: BR
authors.lastname: Bang
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037.
authors.forename: Seung-Goo
authors.initials: SG
authors.lastname: Kang
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037.
authors.forename: Jianhui
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Otsuka
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037.
authors.forename: Jiman
authors.initials: J
authors.lastname: Kang
authors.affiliation: Division of Gastroenterology, BC Children's Hospital, Vancouver, British Columbia, Canada State Key.
authors.forename: Martin
authors.initials: M
authors.lastname: Stahl
authors.affiliation: State Key Laboratory of Cellular Stress Biology and School of Life Sciences, Xiamen University, Xiamen, Fujian, China.
authors.forename: Jiahuai
authors.initials: J
authors.lastname: Han
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037.
authors.forename: Changchun
authors.initials: C
authors.lastname: Xiao
authors.affiliation: Division of Gastroenterology, BC Children's Hospital, Vancouver, British Columbia, Canada State Key.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Vallance
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037.
authors.forename: Young Jun
authors.initials: YJ
authors.lastname: Kang
mesh_terms: D000818:Animals; D044082:Citrobacter rodentium; D003713:Dendritic Cells / Q000201:enzymology / Q000276:immunology; D004195:Disease Models, Animal; D004756:Enterobacteriaceae Infections / Q000201:enzymology* / Q000276:immunology; D004789:Enzyme Activation / Q000276:immunology*; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D005759:Gastroenteritis / Q000201:enzymology / Q000276:immunology; D018928:Immunity, Mucosal / Q000276:immunology*; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008264:Macrophages / Q000201:enzymology / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D048308:Mitogen-Activated Protein Kinase 14 / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000201:enzymology* / Q000276:immunology
chemical_list: D048308:Mitogen-Activated Protein Kinase 14
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