tetano
Editor, Senior Moderator
J Immunol. 2018 Aug 24. pii: ji1800161. doi: 10.4049/jimmunol.1800161. [Epub ahead of print]
[h=1]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.[/h] Kronstad LM[SUP]1[/SUP], Seiler C[SUP]2[/SUP], Vergara R[SUP]3[/SUP], Holmes SP[SUP]2[/SUP], Blish CA[SUP]4,[/SUP][SUP]3,[/SUP][SUP]5[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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/California/07/2009 strain fails to repress the type I IFN response or to downregulate CD54 and CD112 to the same extent, which leads to the enhanced NK cell IFN-γ response. Our results indicate that influenza implements a strain-specific mechanism governing NK cell production of IFN-γ and identifies a previously unrecognized influenza innate immune evasion strategy.
PMID: 30143589 DOI: 10.4049/jimmunol.1800161
[h=1]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.[/h] Kronstad LM[SUP]1[/SUP], Seiler C[SUP]2[/SUP], Vergara R[SUP]3[/SUP], Holmes SP[SUP]2[/SUP], Blish CA[SUP]4,[/SUP][SUP]3,[/SUP][SUP]5[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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/California/07/2009 strain fails to repress the type I IFN response or to downregulate CD54 and CD112 to the same extent, which leads to the enhanced NK cell IFN-γ response. Our results indicate that influenza implements a strain-specific mechanism governing NK cell production of IFN-γ and identifies a previously unrecognized influenza innate immune evasion strategy.
PMID: 30143589 DOI: 10.4049/jimmunol.1800161