Research ArticleVIRAL IMMUNITY

Influenza restriction factor MxA functions as inflammasome sensor in the respiratory epithelium

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Science Immunology  25 Oct 2019:
Vol. 4, Issue 40, eaau4643
DOI: 10.1126/sciimmunol.aau4643

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Influenza and the inflammasome

Influenza A virus (IAV) infection triggers multiple inflammatory responses in the respiratory mucosa, including the release of proinflammatory cytokines like IL-1β through inflammasome activation. The mechanism by which IAV activates inflammasomes has been unclear, but Lee et al. have now identified human myxoma resistance protein 1 (MxA) as an inflammasome sensor protein in human respiratory epithelial cells. MxA recognizes IAV nucleoprotein and interacts with ASC to trigger ASC oligomerization, inflammasome formation, and IL-1β secretion. In transgenic mice expressing human MxA, IAV infection was curbed due to rapid IL-1β secretion in the respiratory epithelium. These findings indicate that MxA can function as an inflammasome sensor during respiratory infection with IAV.

Abstract

The respiratory epithelium is exposed to the environment and initiates inflammatory responses to exclude pathogens. Influenza A virus (IAV) infection triggers inflammatory responses in the respiratory mucosa, but the mechanisms of inflammasome activation are poorly understood. We identified MxA as a functional inflammasome sensor in respiratory epithelial cells that recognizes IAV nucleoprotein and triggers the formation of ASC (apoptosis-associated speck-like protein containing a CARD) specks via interaction of its GTPase domain with the PYD domain of ASC. ASC specks were present in bronchiolar epithelial cells of IAV-infected MxA-transgenic mice, which correlated with early IL-1β production and early recruitment of granulocytes in the lungs of infected mice. Collectively, these results demonstrate that MxA contributes to IAV resistance by triggering a rapid inflammatory response in infected respiratory epithelial cells.

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