title: Stromal IFN-γR-signaling modulates goblet cell function during Salmonella Typhimurium infection.
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-γR)-signaling in mucosal defense. IFN-γ is known to contribute to acute S. Typhimurium diarrhea. We have compared the acute mucosal inflammation in IFN-γR(-/-) mice and wild type animals. IFN-γR(-/-) mice harbored increased pathogen loads in the mucosal epithelium and the lamina propria. Surprisingly, the epithelium of the IFN-γR(-/-) 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-γR-signaling in stromal cells (e.g. goblet cells, enterocytes) controlled mucus excretion/vacuole loss by goblet cells. In contrast, IFN-γR-signaling in bone marrow-derived cells (e.g. macrophages, DCs, PMNs) was required for restricting pathogen growth in the gut tissue. Thus IFN-γR-signaling influences different mucosal responses to infection, including not only pathogen restriction in the lamina propria, but, as shown here, also goblet cell function.
authors.affiliation: Institute of Microbiology (D-BIOL), Eidgenössische Technische Hochschule Zürich, Zürich, Switzerland.
authors.forename: Pascal
authors.initials: P
authors.lastname: Songhet
authors.forename: Manja
authors.initials: M
authors.lastname: Barthel
authors.forename: Bärbel
authors.initials: B
authors.lastname: Stecher
authors.forename: Andreas J
authors.initials: AJ
authors.lastname: Müller
authors.forename: Marcus
authors.initials: M
authors.lastname: Kremer
authors.forename: Gunnar C
authors.initials: GC
authors.lastname: Hansson
authors.forename: Wolf-Dietrich
authors.initials: WD
authors.lastname: Hardt
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D002478:Cells, Cultured; D005455:Fluorescent Antibody Technique; D020397:Goblet Cells / Q000502:physiology*; D007371:Interferon-gamma / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017471:Receptors, Interferon / Q000502:physiology*; D012480:Salmonella Infections / Q000276:immunology* / Q000382:microbiology; D012486:Salmonella typhimurium / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction; D017154:Stromal Cells / Q000276:immunology*; D000096743:Interferon gamma Receptor
chemical_list: D007371:Interferon-gamma; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor