Differential Induction of IFN-α and Modulation of CD112 and CD54 Expression Govern the Magnitude of NK Cell IFN-γ Response to Influenza A Viruses

The Journal of Immunology : Official Journal of the American Association of Immunologists
Lisa M KronstadCatherine A Blish

Abstract

In human and murine studies, IFN-γ is a critical mediator immunity to influenza. IFN-γ production is critical for viral clearance and the development of adaptive immune responses, yet excessive production of IFN-γ and other cytokines as part of a cytokine storm is associated with poor outcomes of influenza infection in humans. As NK cells are the main population of lung innate immune cells capable of producing IFN-γ early in infection, we set out to identify the drivers of the human NK cell IFN-γ response to influenza A viruses. We found that influenza triggers NK cells to secrete IFN-γ in the absence of T cells and in a manner dependent upon signaling from both cytokines and receptor-ligand interactions. Further, we discovered that the pandemic A/California/07/2009 (H1N1) strain elicits a seven-fold greater IFN-γ response than other strains tested, including a seasonal A/Victoria/361/2011 (H3N2) strain. These differential responses were independent of memory NK cells. Instead, we discovered that the A/Victoria/361/2011 influenza strain suppresses the NK cell IFN-γ response by downregulating NK-activating ligands CD112 and CD54 and by repressing the type I IFN response in a viral replication-dependent manner. In contrast, the A...Continue Reading

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Citations

May 7, 2019·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Axel R SchulzHenrik E Mei
May 23, 2019·The Journal of Infectious Diseases·Monika Redlberger-FritzElisabeth Puchhammer-Stöckl
Nov 12, 2019·Frontiers in Immunology·Mathieu Le GarsCatherine A Blish
May 12, 2019·Science Immunology·Rana NikzadSilke Paust
May 12, 2020·Frontiers in Immunology·Thanmayi RanganathCatherine A Blish
Aug 18, 2020·Proceedings of the National Academy of Sciences of the United States of America·Zicheng HuAtul J Butte
Nov 5, 2019·Frontiers in Immunology·Ronald P SchuylerElena W Y Hsieh
Sep 26, 2020·Frontiers in Cellular and Infection Microbiology·Kayla Frank, Silke Paust
Nov 17, 2020·Frontiers in Cellular and Infection Microbiology·Saskia L van der HeideJohn W Upham
Dec 3, 2020·Frontiers of Medicine·Qian XuGang Huang
Nov 3, 2020·Clinical and Translational Medicine·Ting ZhangXianting Ding
Mar 17, 2019·Current Opinion in Virology·Ayad AliStephen N Waggoner
Mar 24, 2021·BMC Bioinformatics·Christof SeilerSusan Holmes

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