- Authors: Duerr, C. U., Zenk, S. F., Chassin, C., Pott, J., Gutle, D., Hensel, M., Hornef, M. W.
- Year: 2009
- Journal: PLoS Pathog 5 e1000567
- Applications: in vitro / Protein/Peptide/Antibody, siRNA / INTERFERin, PULSin
- Cell types:
- Name: m-ICcl2
- Name: RAW 264.7
Description: Mouse monocytes/macrophages
Known as: RAW
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.