title: O-antigen delays lipopolysaccharide recognition and impairs antibacterial host defense in murine intestinal epithelial cells.
abstract: Although Toll-like receptor (TLR) 4 signals from the cell surface of myeloid cells, it is restricted to an intracellular compartment and requires ligand internalization in intestinal epithelial cells (IECs). Yet, the functional consequence of cell-type specific receptor localization and uptake-dependent lipopolysaccharide (LPS) recognition is unknown. Here, we demonstrate a strikingly delayed activation of IECs but not macrophages by wildtype Salmonella enterica subsp. enterica sv. (S.) Typhimurium as compared to isogenic O-antigen deficient mutants. Delayed epithelial activation is associated with impaired LPS internalization and retarded TLR4-mediated immune recognition. The O-antigen-mediated evasion from early epithelial innate immune activation significantly enhances intraepithelial bacterial survival in vitro and in vivo following oral challenge. These data identify O-antigen expression as an innate immune evasion mechanism during apical intestinal epithelial invasion and illustrate the importance of early innate immune recognition for efficient host defense against invading Salmonella.
authors.affiliation: Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany.
authors.forename: Claudia U
authors.initials: CU
authors.lastname: Duerr
authors.forename: Sebastian F
authors.initials: SF
authors.lastname: Zenk
authors.forename: Cécilia
authors.initials: C
authors.lastname: Chassin
authors.forename: Johanna
authors.initials: J
authors.lastname: Pott
authors.forename: Dominique
authors.initials: D
authors.lastname: Gütle
authors.forename: Michael
authors.initials: M
authors.lastname: Hensel
authors.forename: Mathias W
authors.initials: MW
authors.lastname: Hornef
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism; D054426:Chemokine CXCL2 / Q000378:metabolism; D003627:Data Interpretation, Statistical; D004847:Epithelial Cells / Q000276:immunology; D005260:Female; D054884:Host-Pathogen Interactions / Q000276:immunology; D007113:Immunity, Innate; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology*; D007700:Kinetics; D008070:Lipopolysaccharides / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D019081:O Antigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D012475:Salmonella / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D012486:Salmonella typhimurium / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity; D051197:Toll-Like Receptor 4 / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D054426:Chemokine CXCL2; C404915:Cxcl2 protein, mouse; D008070:Lipopolysaccharides; D016328:NF-kappa B; D019081:O Antigens; C419942:Spi1 protein, Salmonella; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4