Pathogen-specific TLR signaling in mucosa: mutual contribution of microbial TLR agonists and virulence factors.
Detection of microorganisms through microbe-associated molecular patterns (MAMP) by Toll-like receptors (TLR) is crucial to trigger protective immunity. In the mucosa, sentinel cells are exposed to MAMP from both pathogens and commensals; however, the TLR response is tightly controlled to avoid inflammation in response to commensals. Uropathogenic Escherichia coli (UPEC) trigger innate responses during urinary tract infection in a TLR4-dependent and CD14-independent manner. UPEC express virulence factors, such as type 1 fimbriae and/or P fimbriae, allowing bacterial attachment to the epithelium. In this issue of the European Journal of Immunology, Fisher et al. show that fimbriae are required to induce a TLR4-specific epithelial response. Depending on the fimbriae expressed by UPEC, different adaptor molecules are involved in TLR4 signaling. These data add to the recent body of evidence suggesting that TLR responses are regulated by co-receptors, such as receptors for virulence factors. In conclusion, the "pathogenic" TLR stimulation provides a novel way for the host to ignore commensal bacteria.
Sirard
Jean-Claude
JC
INSERM, Avenir Anti-microbial mucosal Immunity - E364, Campus Pasteur - Lille, France. Jean-Claude.Sirard@ibl.fr
Bayardo
Mariela
M
Didierlaurent
Arnaud
A
D000818:Animals; D004926:Escherichia coli / Q000276:immunology* / Q000472:pathogenicity; D004927:Escherichia coli Infections / Q000276:immunology*; D006801:Humans; D018928:Immunity, Mucosal / Q000276:immunology*; D009092:Mucous Membrane / Q000276:immunology / Q000382:microbiology; D015398:Signal Transduction / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000276:immunology*; D014552:Urinary Tract Infections / Q000276:immunology*; D037521:Virulence Factors / Q000276:immunology
C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D037521:Virulence Factors