Kronstad LM, Seiler C, Vergara R, Holmes SP. 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. J Immunol. 2018 Aug 24. pii: ji1800161.
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.
See Also:
Latest articles in those days:
- Dairy producers´ perceptions of highly pathogenic avian influenza (HPAI) H5N1 and their influence on implementation of biosecurity changes 21 hours ago
- Genetic Characterization of Highly Similar H9N2 Viruses Isolated from Swine and Poultry in China 21 hours ago
- Influenza disease burden investigation and cost-effectiveness analysis based on system dynamics model 1 days ago
- Descriptive analysis of dairy cow imports from the United States into Ontario, Canada between 2009 and 2019: implications for the risk of H5N1 introduction 1 days ago
- Pre-existing cross-subtype serological responses against H5Nx in health care workers 1 days ago
[Go Top] [Close Window]


