O-Antigen Delays Lipopolysaccharide Recognition and Impairs Antibacterial Host Defense in Murine Intestinal Epithelial Cells |
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| Authors: | Claudia U Duerr Sebastian F Zenk Cécilia Chassin Johanna Pott Dominique Gütle Michael Hensel Mathias W Hornef |
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| Institution: | 1. Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany.; 2. Institute for Microbiology, University Hospital Erlangen, Erlangen, Germany.; 3. Division of Infection Biology, University Hospital Erlangen, Erlangen, Germany.;University of Toronto, Canada |
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| 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. |
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