RT Journal Article
SR Electronic
T1 Strain-Specific Human Natural Killer Cell Recognition of Influenza A Virus
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 148528
DO 10.1101/148528
A1 Lisa M. Kronstad
A1 Christof Seiler
A1 Rosemary Vergara
A1 Susan P. Holmes
A1 Catherine A. Blish
YR 2017
UL http://biorxiv.org/content/early/2017/06/10/148528.abstract
AB Abstract Innate Natural killer (NK) cells employ an array of surface receptors to detect ‘altered self’ induced by infection or malignancy. Despite their decisive role in early antiviral immunity, the cellular mechanisms governing if or how they discriminate between viral infections remain unresolved. Here, we demonstrate that while human NK cells are capable of reducing infection levels of distinct influenza A strains, the A/California/07/2009 (pH1N1) strain induces a significantly more robust IFN-γ response than A/Victoria/361/2011 (H3N2) and all other strains tested. This surprising degree of strain specificity results in part from the inability of the pH1N1 strain to downregulate the activating ligands CD112 (Nectin-2) and CD54 (ICAM-1) as efficiently as the H3N2 strain, leading to enhanced NK cell detection and IFN-γ secretion. A network analysis of differentially expressed transcripts identifies the interferon α/β receptor (IFNAR) pathway as an additional, critical determinant of this strain-specific response. Strain-specific downregulation of NK cell activating ligands and modulation of type I IFN production represents a previously unrecognized influenza immunoevasion tactic and could present new opportunities to modulate the quality and quantity of the innate antiviral response for therapeutic benefit.One Sentence Summary Human natural killer cells distinguish between Influenza A strains using a combinatorial cytokine priming and receptor-ligand signaling mechanism.