O-Antigen Delays Lipopolysaccharide Recognition and Impairs Antibacterial Host Defense in Murine Intestinal Epithelial Cells

PLoS Pathogens

Michael Hensel¹  Claudia U. Duerr²  Mathias W. Hornef²  Johanna Pott²  Dominique Gütle²  Cécilia Chassin²  Sebastian F. Zenk³ 

[1] Division of Infection Biology, University Hospital Erlangen, Erlangen, Germany;Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany;Institute for Microbiology, University Hospital Erlangen, Erlangen, Germany

关键词: Salmonella;    Salmonellosis;    Salmonella typhimurium;    Epithelial cells;    Intracellular pathogens;    Gastrointestinal tract;    Macrophages;    Complement system;   

DOI  :  10.1371/journal.ppat.1000567

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY