Influenza restriction factor MxA functions as inflammasome sensor in the respiratory epithelium
Open Access
- 11 October 2019
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science Immunology
- Vol. 4 (40)
- https://doi.org/10.1126/sciimmunol.aau4643
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.Keywords
Funding Information
- Japan Agency for Medical Research and Development (JP18fk0108076)
- Deutsche Forschungsgemeinschaft (SFB 1160)
- Ministry of Education, Culture, Sports, Science, and Technology (16H05192)
- Ministry of Education, Culture, Sports, Science, and Technology (24115002)
- Ministry of Education, Culture, Sports, Science, and Technology (19H03475)
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