Alpizar, Yeranddy A.Boonen, BrettSánchez, AliciaJung, CaroleLópez-Requena, AlejandroNaert, RobbeSteelant, BrechtLuyts, KatrienPlata, CristinaVooght, Vanessa DeVanoirbeek, Jeroen A.J.Meseguer, Victor M.Voets, ThomasAlvarez, Julio L.Hellings, Peter W.Hoet, Peter H.M.Nemery, BenoitValverde, M. A. (Miguel Ángel), 1963-Talavera, Karel2017-11-102017-11-102017Alpizar YA, Boonen B, Sanchez A, Jung C, López-Requena A, Naert R. TRPV4 activation triggers protective responses to bacterial lipopolysaccharides in airway epithelial cells. Nat Commun. 2017 Oct 20;8(1):1059. DOI: 10.1038/s41467-017-01201-32041-1723http://hdl.handle.net/10230/33185Lipopolysaccharides (LPS), the major components of the wall of gram-negative bacteria, trigger powerful defensive responses in the airways via mechanisms thought to rely solely on the Toll-like receptor 4 (TLR4) immune pathway. Here we show that airway epithelial cells display an increase in intracellular Ca2+ concentration within seconds of LPS application. This response occurs in a TLR4-independent manner, via activation of the transient receptor potential vanilloid 4 cation channel (TRPV4). We found that TRPV4 mediates immediate LPS-induced increases in ciliary beat frequency and the production of bactericidal nitric oxide. Upon LPS challenge TRPV4-deficient mice display exacerbated ventilatory changes and recruitment of polymorphonuclear leukocytes into the airways. We conclude that LPS-induced activation of TRPV4 triggers signaling mechanisms that operate faster and independently from the canonical TLR4 immune pathway, leading to immediate protective responses such as direct antimicrobial action, increase in airway clearance, and the regulation of the inflammatory innate immune reaction.application/pdfeng© Nature Publishing Group. http://dx.doi.org/10.1038/s41467-017-01201-3 This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were madePolisacàridsGenètica bacterianaGenèticainfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/s41467-017-01201-3info:eu-repo/semantics/openAccess