Cutting Edge: Influenza A virus activates TLR3-dependent inflammatory and RIG-I-dependent antiviral responses in human lung epithelial cells.
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.
Le Goffic
Ronan
R
Unité de Défense Innée et Inflammation, INSERM Unité 874, Institut Pasteur, 25 Rue du Dr. Roux, 75015 Paris, France.
Pothlichet
Julien
J
Vitour
Damien
D
Fujita
Takashi
T
Meurs
Eliane
E
Chignard
Michel
M
Si-Tahar
Mustapha
M
D002460:Cell Line; D053487:DEAD-box RNA Helicases / Q000276:immunology; D004847:Epithelial Cells / Q000276:immunology* / Q000821:virology; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology; D053122:Influenza A Virus, H3N2 Subtype; D007251:Influenza, Human / Q000235:genetics / Q000276:immunology*; D007370:Interferon Type I / Q000276:immunology; D000072640:Interferon-Induced Helicase, IFIH1; D008168:Lung / Q000276:immunology*; D024101:Mitochondrial Proteins / Q000276:immunology; D020365:RNA Helicases; D012330:RNA, Double-Stranded / Q000276:immunology; D012367:RNA, Viral / Q000276:immunology; D018168:Receptors, Retinoic Acid / Q000276:immunology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D051196:Toll-Like Receptor 3 / Q000235:genetics / Q000276:immunology*
D007370:Interferon Type I; D024101:Mitochondrial Proteins; C437968:PLAAT4 protein, human; D012330:RNA, Double-Stranded; D012367:RNA, Viral; D018168:Receptors, Retinoic Acid; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; C452815:IFIH1 protein, human; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1; D020365:RNA Helicases