tetano
Editor, Senior Moderator
Sci Immunol. 2019 Oct 25;4(40). pii: eaau4643. doi: 10.1126/sciimmunol.aau4643. [h=1]Influenza restriction factor MxA functions as inflammasome sensor in the respiratory epithelium.[/h]
Lee S[SUP]1[/SUP], Ishitsuka A[SUP]2[/SUP], Noguchi M[SUP]3[/SUP], Hirohama M[SUP]1[/SUP], Fujiyasu Y[SUP]4[/SUP], Petric PP[SUP]5,[/SUP][SUP]6,[/SUP][SUP]7[/SUP], Schwemmle M[SUP]5,[/SUP][SUP]6[/SUP], Staeheli P[SUP]5,[/SUP][SUP]6[/SUP], Nagata K[SUP]1[/SUP], Kawaguchi A[SUP]8,[/SUP][SUP]2,[/SUP][SUP]9,[/SUP][SUP]10[/SUP].
[h=3]Author information[/h] 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.
[h=3]Abstract[/h] 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
Lee S[SUP]1[/SUP], Ishitsuka A[SUP]2[/SUP], Noguchi M[SUP]3[/SUP], Hirohama M[SUP]1[/SUP], Fujiyasu Y[SUP]4[/SUP], Petric PP[SUP]5,[/SUP][SUP]6,[/SUP][SUP]7[/SUP], Schwemmle M[SUP]5,[/SUP][SUP]6[/SUP], Staeheli P[SUP]5,[/SUP][SUP]6[/SUP], Nagata K[SUP]1[/SUP], Kawaguchi A[SUP]8,[/SUP][SUP]2,[/SUP][SUP]9,[/SUP][SUP]10[/SUP].
[h=3]Author information[/h] 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.
[h=3]Abstract[/h] 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