%0 Journal Article %T TLR2/MyD88/NF-¦ÊB Pathway, Reactive Oxygen Species, Potassium Efflux Activates NLRP3/ASC Inflammasome during Respiratory Syncytial Virus Infection %A Jesus Segovia %A Ahmed Sabbah %A Victoria Mgbemena %A Su-Yu Tsai %A Te-Hung Chang %A Michael T. Berton %A Ian R. Morris %A Irving C. Allen %A Jenny P.-Y. Ting %A Santanu Bose %J PLOS ONE %D 2012 %I Public Library of Science (PLoS) %R 10.1371/journal.pone.0029695 %X Human respiratory syncytial virus (RSV) constitute highly pathogenic virus that cause severe respiratory diseases in newborn, children, elderly and immuno-compromised individuals. Airway inflammation is a critical regulator of disease outcome in RSV infected hosts. Although ¡°controlled¡± inflammation is required for virus clearance, aberrant and exaggerated inflammation during RSV infection results in development of inflammatory diseases like pneumonia and bronchiolitis. Interleukin-1¦Â (IL-1¦Â) plays an important role in inflammation by orchestrating the pro-inflammatory response. IL-1¦Â is synthesized as an immature pro-IL-1¦Â form. It is cleaved by activated caspase-1 to yield mature IL-1¦Â that is secreted extracellularly. Activation of caspase-1 is mediated by a multi-protein complex known as the inflammasome. Although RSV infection results in IL-1¦Â release, the mechanism is unknown. Here in, we have characterized the mechanism of IL-1¦Â secretion following RSV infection. Our study revealed that NLRP3/ASC inflammasome activation is crucial for IL-1¦Â production during RSV infection. Further studies illustrated that prior to inflammasome formation; the ¡°first signal¡± constitutes activation of toll-like receptor-2 (TLR2)/MyD88/NF-¦ÊB pathway. TLR2/MyD88/NF-¦ÊB signaling is required for pro-IL-1¦Â and NLRP3 gene expression during RSV infection. Following expression of these genes, two ¡°second signals¡± are essential for triggering inflammasome activation. Intracellular reactive oxygen species (ROS) and potassium (K+) efflux due to stimulation of ATP-sensitive ion channel promote inflammasome activation following RSV infection. Thus, our studies have underscored the requirement of TLR2/MyD88/NF-¦ÊB pathway (first signal) and ROS/potassium efflux (second signal) for NLRP3/ASC inflammasome formation, leading to caspase-1 activation and subsequent IL-1¦Â release during RSV infection. %U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0029695