%0 Journal Article
%T Inflammasome activation is required for human rhinovirus-induced airway inflammation in naive and allergen-sensitized mice
%J -
%D 2019
%R https://doi.org/10.1038/s41385-019-0172-2
%X Activation of the inflammasome is a key function of the innate immune response that regulates inflammation in response to microbial substances. Inflammasome activation by human rhinovirus (RV), a major cause of asthma exacerbations, has not been well studied. We examined whether RV induces inflammasome activation in vivo, molecular mechanisms underlying RV-stimulated inflammasome priming and activation, and the contribution of inflammasome activation to RV-induced airway inflammation and exacerbation. RV infection triggered lung mRNA and protein expression of pro-IL-1¦Â and NLRP3, indicative of inflammasome priming, as well as cleavage of caspase-1 and pro-IL-1¦Â, completing inflammasome activation. Immunofluorescence staining showed IL-1¦Â in lung macrophages. Depletion with clodronate liposomes and adoptive transfer experiments showed macrophages to be required and sufficient for RV-induced inflammasome activation. TLR2 was required for RV-induced inflammasome priming in vivo. UV irradiation blocked inflammasome activation and RV genome was sufficient for inflammasome activation in primed cells. Naive and house dust mite-treated NLRP3£¿/£¿ and IL-1¦Â£¿/£¿ mice, as well as IL-1 receptor antagonist-treated mice, showed attenuated airway inflammation and responsiveness following RV infection. We conclude that RV-induced inflammasome activation is required for maximal airway inflammation and hyperresponsiveness in naive and allergic mice. The inflammasome represents a molecular target for RV-induced asthma exacerbations
%U https://www.nature.com/articles/s41385-019-0172-2