TLR 5, but neither TLR2 nor TLR4, is involved in lung epithelial cell response to Burkholderia cenocepacia.
Burkholderia cenocepacia is known to induce a harmful inflammatory response in the airways of cystic fibrosis patients. Toll-like receptors (TLRs) play key roles in sensing microbial-associated molecular patterns and initiating host innate immunity, but their role in the inflammatory response elicited by B. cenocepacia has not been precisely examined. In this study, we evaluated the contribution of TLR2, TLR4 and TLR5 to the signaling pathways triggered by B. cenocepacia in human bronchial epithelial cells. By quantitative reverse transcriptase (RT)-PCR, we demonstrated that the expression of both TLR2 and TLR4 was significantly upregulated by B. cenocepacia infection, whereas TLR5 expression remained unchanged. Using a dominant-negative approach and airway epithelial cells isolated from MyD88(-/-) mice, we found that B. cenocepacia activated a signaling complex that required the adapter molecule MyD88. Moreover, using epithelial cells from TLR2(-/-), TLR4(-/-) or TLR2/4(-/-) mice or cells overexpressing a functional form of TLR5, we established that TLR5, but neither TLR2 nor TLR4, critically regulated B. cenocepacia-induced lung epithelial inflammatory response.
de C Ventura
Grasiella M
GM
Institut Pasteur, Unité de Défense Innée et Inflammation, Paris, France.
Le Goffic
Ronan
R
Balloy
Viviane
V
Plotkowski
Maria-Cristina
MC
Chignard
Michel
M
Si-Tahar
Mustapha
M
D000818:Animals; D019117:Burkholderia / Q000145:classification / Q000472:pathogenicity*; D002460:Cell Line; D004847:Epithelial Cells / Q000276:immunology / Q000382:microbiology; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation / Q000276:immunology* / Q000382:microbiology; D008168:Lung / Q000166:cytology / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D015398:Signal Transduction; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D051198:Toll-Like Receptor 5 / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; C495346:TLR5 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051198:Toll-Like Receptor 5