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Cutting edge: innate immune response triggered by influenza A virus is negatively regulated by SOCS1 and SOCS3 through a RIG-I/IFNAR1-dependent pathway

Abstract : Influenza A virus (IAV) triggers a contagious respiratory disease that produces considerable lethality. Although this lethality is likely due to an excessive host inflammatory response, the negative feedback mechanisms aimed at regulating such a response are unknown. In this study, we investigated the role of the eight "suppressor of cytokine signaling" (SOCS) regulatory proteins in IAV-triggered cytokine expression in human respiratory epithelial cells. SOCS1 to SOCS7, but not cytokine-inducible Src homology 2-containing protein (CIS), are constitutively expressed in these cells and only SOCS1 and SOCS3 expressions are up-regulated upon IAV challenge. Using distinct approaches affecting the expression and/or the function of the IFNalphabeta receptor (IFNAR)1, the viral sensors TLR3 and retinoic acid-inducible gene I (RIG-I) as well as the mitochondrial antiviral signaling protein (MAVS, a RIG-I signaling intermediate), we demonstrated that SOCS1 and SOCS3 up-regulation requires a TLR3-independent, RIG-I/MAVS/IFNAR1-dependent pathway. Importantly, by using vectors overexpressing SOCS1 and SOCS3 we revealed that while both molecules inhibit antiviral responses, they differentially modulate inflammatory signaling pathways.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-00206322
Contributor : Mustapha Si-Tahar <>
Submitted on : Thursday, January 17, 2008 - 9:59:27 AM
Last modification on : Monday, January 13, 2020 - 5:08:06 PM
Long-term archiving on: : Friday, November 25, 2016 - 7:58:07 PM

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Julien Pothlichet, Michel Chignard, Mustapha Si-Tahar. Cutting edge: innate immune response triggered by influenza A virus is negatively regulated by SOCS1 and SOCS3 through a RIG-I/IFNAR1-dependent pathway. Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, 2008, 180 (4), pp.2034-2038. ⟨10.4049/jimmunol.180.4.2034⟩. ⟨pasteur-00206322⟩

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