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CUTTING EDGE |
* Institut Pasteur, Unité de Défense Innée et Inflammation, Paris, France;
Institut National de la Santé et de la Recherche Médicale Unité 874, Paris, France;
Institut Pasteur, Unité Postulante des Hépacivirus, Paris, France; and
Department of Tumor Cell Biology, The Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan
Influenza A virus (IAV) triggers a contagious acute respiratory disease that causes considerable mortality annually. Recently, we established a role for the pattern-recognition TLR3 in the response of lung epithelial cells to IAV-derived dsRNA. However, additional nucleic acid-recognition proteins have lately been implicated as key viral sensors, including the RNA helicases retinoic acid-inducible gene-I (RIG-I) and melanoma differentiation-associated gene (MDA)-5. In this study, we investigated the respective role of TLR3 vs RIG-I/MDA-5 signaling in human respiratory epithelial cells infected by IAV using BEAS-2B cells transfected with vectors encoding either a dominant-negative form of TLR3 or of mitochondrial antiviral signaling protein (MAVS; a signaling intermediate of RIG-I and MDA-5), or with plasmids overexpressing functional RIG-I or MDA-5. We demonstrate that the sensing of IAV by TLR3 primarily regulates a proinflammatory response, whereas RIG-I (but not MDA-5) mediates both a type I IFN-dependent antiviral signaling and a proinflammatory response.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was partially funded by the Institut Pasteur through a Programme Transversal de Recherche (Grant 186). Part of the work was also generously supported by the Société de Pneumologie de Langue Française. R.L.G. is a recipient of a Bourse Roux awarded by the Institut Pasteur. J.P. and D.V. were financially supported by the French association Vaincre la Mucoviscidose and by the Agence Nationale de la Recherche sur le Sida, respectively.
2 Address correspondence and reprint requests to Dr. Mustapha Si-Tahar, Unité de Défense Innée et Inflammation, Institut National de la Santé et de la Recherche Médicale Unité 874, Institut Pasteur, 25 rue du Dr. Roux, 75015 Paris, France. E-mail address: sitahar{at}pasteur.fr
3 Abbreviations used in this paper: IAV, influenza A virus; CARD, caspase recruiting domain; MAVS, mitochondrial antiviral signaling protein; MOI, multiplicity of infection; IRF, IFN regulatory factor; DC, dendritic cell.
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