stromal ifn-γr-signaling modulates goblet cell function during salmonella typhimurium infection基质ifn-γr-signaling调节杯状细胞功能在鼠伤寒沙门氏菌感染.pdfVIP

Stromal IFN-cR-Signaling Modulates Goblet Cell Function During Salmonella Typhimurium Infection 1 1 ¨ 1¤a ¨ 1¤b 2 Pascal Songhet , Manja Barthel , Barbel Stecher , Andreas J. Muller , Marcus Kremer , Gunnar C. 3 1 Hansson , Wolf-Dietrich Hardt * ¨ ¨ ¨ ¨ 1 Institute of Microbiology (D-BIOL), Eidgenossische Technische Hochschule Zurich, Zurich, Switzerland, 2 Institut fur Allgemeine Pathologie und Pathologische Anatomie, ¨ ¨ Technische Universitat Munchen, Munich, Germany, 3 Department of Medical Biochemistry, University of Gothenburg, Gothenburg, Sweden Abstract Enteropathogenic bacteria are a frequent cause of diarrhea worldwide. The mucosal defenses against infection are not completely understood. We have used the streptomycin mouse model for Salmonella Typhimurium diarrhea to analyze the role of interferon gamma receptor (IFN-cR)-signaling in mucosal defense. IFN-c is known to contribute to acute S. Typhimurium diarrhea. We have compared the acute mucosal inflammation in IFN-cR-/- mice and wild type animals. IFN-cR-/- mice harbored increased pathogen loads in the mucosal epithelium and the lamina propria. Surprisingly, the epithelium of the IFN-cR-/- mice did not show the dramatic ‘‘loss’’ of mucus-filled goblet cell vacuoles, a hallmark of the wild type mucosal infection. Using bone marrow chimeric mice we established that IFN-cR-signaling in stromal cells (e.g. goblet cells, enterocytes) controlled mucus excretion/vacuole l