title: Salmonella gut invasion involves TTSS-2-dependent epithelial traversal, basolateral exit, and uptake by epithelium-sampling lamina propria phagocytes.
abstract: Salmonella Typhimurium causes diarrhea by infecting the epithelium and lamina propria of the intestinal mucosa and by secreting various effector proteins through type III secretion systems (TTSSs). However, the mechanisms by which Salmonella transverses the epithelium and is subsequently released into the lamina propria are poorly understood. Using a murine Salmonella-diarrhea model and in vivo microscopy, we show that epithelial traversal requires TTSS-1-mediated invasion and TTSS-2-dependent trafficking to the basolateral side. After being released into the lamina propria, the bacterium is transiently extracellular before being taken up by phagocytes, including CD11c(+)CX(3)CR1(high) monocytic phagocytes (MPs), which were found to constitutively sample cellular material shed from the basolateral side of the epithelium. Thus, Salmonella infects the cecal mucsa through a step-wise process wherein the bacterium transverses the epithelium through TTSS-2-dependent trafficking and then likely exploits lamina propria MPs, which are sampling the epithelium, to enter and replicate within the host.
authors.affiliation: Institute of Microbiology, D-BIOL, ETH Zürich, 8093 Zürich, Switzerland.
authors.forename: Andreas J
authors.initials: AJ
authors.lastname: Müller
authors.forename: Patrick
authors.initials: P
authors.lastname: Kaiser
authors.forename: Kurt E J
authors.initials: KE
authors.lastname: Dittmar
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Weber
authors.forename: Sabine
authors.initials: S
authors.lastname: Haueter
authors.forename: Kathrin
authors.initials: K
authors.lastname: Endt
authors.forename: Pascal
authors.initials: P
authors.lastname: Songhet
authors.forename: Christa
authors.initials: C
authors.lastname: Zellweger
authors.forename: Marcus
authors.initials: M
authors.lastname: Kremer
authors.forename: Hans-Jörg
authors.initials: HJ
authors.lastname: Fehling
authors.forename: Wolf-Dietrich
authors.initials: WD
authors.lastname: Hardt
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004848:Epithelium / Q000382:microbiology*; D041981:Gastrointestinal Tract / Q000382:microbiology*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D051379:Mice; D008853:Microscopy; D009092:Mucous Membrane / Q000166:cytology / Q000382:microbiology*; D010586:Phagocytes / Q000382:microbiology*; D012481:Salmonella Infections, Animal; D012486:Salmonella typhimurium / Q000472:pathogenicity*; D037521:Virulence Factors / Q000378:metabolism*
chemical_list: D026901:Membrane Transport Proteins; D037521:Virulence Factors