title: Age-dependent enterocyte invasion and microcolony formation by Salmonella.
abstract: The coordinated action of a variety of virulence factors allows Salmonella enterica to invade epithelial cells and penetrate the mucosal barrier. The influence of the age-dependent maturation of the mucosal barrier for microbial pathogenesis has not been investigated. Here, we analyzed Salmonella infection of neonate mice after oral administration. In contrast to the situation in adult animals, we observed spontaneous colonization, massive invasion of enteroabsorptive cells, intraepithelial proliferation and the formation of large intraepithelial microcolonies. Mucosal translocation was dependent on enterocyte invasion in neonates in the absence of microfold (M) cells. It further resulted in potent innate immune stimulation in the absence of pronounced neutrophil-dominated pathology. Our results identify factors of age-dependent host susceptibility and provide important insight in the early steps of Salmonella infection in vivo. We also present a new small animal model amenable to genetic manipulation of the host for the analysis of the Salmonella enterocyte interaction in vivo.
authors.affiliation: Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany.
authors.forename: Kaiyi
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany.
authors.forename: Aline
authors.initials: A
authors.lastname: Dupont
authors.affiliation: Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany.
authors.forename: Natalia
authors.initials: N
authors.lastname: Torow
authors.forename: Frederik
authors.initials: F
authors.lastname: Gohde
authors.affiliation: Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Gohde
authors.affiliation: Department of Molecular Immunology, Helmholtz Centre for Infection Research (HZI), Braunschweig, Germany.
authors.forename: Sara
authors.initials: S
authors.lastname: Leschner
authors.affiliation: Department of Molecular Immunology, Helmholtz Centre for Infection Research (HZI), Braunschweig, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Lienenklaus
authors.affiliation: Department of Molecular Immunology, Helmholtz Centre for Infection Research (HZI), Braunschweig, Germany.
authors.forename: Siegfried
authors.initials: S
authors.lastname: Weiss
authors.affiliation: Department of Viral Immune Modulation, Helmholtz Centre for Infection Research (HZI), Braunschweig, Germany.
authors.forename: Melanie M
authors.initials: MM
authors.lastname: Brinkmann
authors.affiliation: Centre for Anatomy, Hannover Medical School, Hannover, Germany.
authors.forename: Mark
authors.initials: M
authors.lastname: Kühnel
authors.affiliation: Division of Microbiology, University of Osnabrück, Osnabrück, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Hensel
authors.affiliation: Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Fulde
authors.affiliation: Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany.
authors.forename: Mathias W
authors.initials: MW
authors.lastname: Hornef
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D020895:Enterocytes / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D004847:Epithelial Cells / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D015964:Gene Expression Regulation, Bacterial; D008264:Macrophages / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D012481:Salmonella Infections, Animal / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D012486:Salmonella typhimurium / Q000472:pathogenicity*; D014774:Virulence / Q000276:immunology*
chemical_list: D001426:Bacterial Proteins