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

[tetano]

Sci Immunol. 2019 Oct 25;4(40). pii: eaau4643. doi: 10.1126/sciimmunol.aau4643. Influenza restriction factor MxA functions as inflammasome sensor in the respiratory epithelium.

Lee S¹, Ishitsuka A², Noguchi M³, Hirohama M¹, Fujiyasu Y⁴, Petric PP^5,6,7, Schwemmle M^5,6, Staeheli P^5,6, Nagata K¹, Kawaguchi A^8,2,9,10.
Author information

1 Department of Infection Biology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan. 2 PhD Program in Human Biology, School of Integrative and Global Majors, University of Tsukuba, Tsukuba, Japan. 3 Department of Pathology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan. 4 School of Medicine, University of Tsukuba, Tsukuba, Japan. 5 Institute of Virology, University Medical Center Freiburg, Freiburg, Germany. 6 Faculty of Medicine, University of Freiburg, Freiburg, Germany. 7 Spemann Graduate School of Biology and Medicine, University of Freiburg, Freiburg, Germany. 8 Department of Infection Biology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan. ats-kawaguchi@md.tsukuba.ac.jp. 9 Transborder Medical Research Center, University of Tsukuba, Tsukuba, Japan. 10 Microbiology Research Center for Sustainability, University of Tsukuba, Tsukuba, Japan.

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.
Copyright ? 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.


PMID: 31653718 DOI: 10.1126/sciimmunol.aau4643