title: Gamma interferon produced by antigen-specific CD4+ T cells regulates the mucosal immune responses to Citrobacter rodentium infection.
abstract: Citrobacter rodentium, a murine model pathogen for enteropathogenic Escherichia coli, colonizes the surface of intestinal epithelial cells and causes mucosal inflammation. This bacterium is an ideal model for investigating pathogen-host immune interactions in the gut. It is well known that gene transcripts for Th1 cytokines are highly induced in colonic tissue from mice infected with C. rodentium. However, it remains to be seen whether the Th1 or Th2 cytokines produced by antigen-specific CD4(+) T cells provide effective regulation of the host immune defense against C. rodentium infection. To investigate the antigen-specific immune responses, C. rodentium expressing ovalbumin (OVA-C. rodentium), a model antigen, was generated and used to define antigen-specific responses under gamma interferon (IFN-gamma)-deficient or interleukin-4 (IL-4)-deficient conditions in vivo. The activation of antigen-specific CD4(+) T cells and macrophage phagocytosis were evaluated in the presence of IFN-gamma or IL-4 in vitro. IFN-gamma-deficient mice exhibited a loss of body weight and a higher bacterial concentration in feces during OVA-C. rodentium infection than C57BL/6 (wild type) or IL-4-deficient mice. This occurred through the decreased efficiency of macrophage phagocytosis and the activation of antigen-specific CD4(+) T cells. Furthermore, a deficiency in antigen-specific CD4(+) T-cell-expressed IFN-gamma led to a higher susceptibility to mucosal and gut-derived systemic OVA-C. rodentium infection. These results show that the IFN-gamma produced by antigen-specific CD4(+) T cells plays an important role in the defense against C. rodentium.
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Shiomi
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Masuda
authors.forename: Shin
authors.initials: S
authors.lastname: Nishiumi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Nishida
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Takagawa
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Shiomi
authors.forename: Hiromu
authors.initials: H
authors.lastname: Kutsumi
authors.forename: Richard S
authors.initials: RS
authors.lastname: Blumberg
authors.forename: Takeshi
authors.initials: T
authors.lastname: Azuma
authors.forename: Masaru
authors.initials: M
authors.lastname: Yoshida
mesh_terms: D000818:Animals; D001835:Body Weight; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D044082:Citrobacter rodentium / Q000276:immunology*; D004756:Enterobacteriaceae Infections / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D005243:Feces / Q000382:microbiology; D005260:Female; D018928:Immunity, Mucosal; D007371:Interferon-gamma / Q000172:deficiency / Q000276:immunology*; D015847:Interleukin-4 / Q000172:deficiency / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D010587:Phagocytosis
chemical_list: D015847:Interleukin-4; D007371:Interferon-gamma; D010047:Ovalbumin