O-antigen delays lipopolysaccharide recognition and impairs antibacterial host defense in murine intestinal epithelial cells.
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.
Duerr
Claudia U
CU
Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany.
Zenk
Sebastian F
SF
Chassin
Cécilia
C
Pott
Johanna
J
Gütle
Dominique
D
Hensel
Michael
M
Hornef
Mathias W
MW
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
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