Natural killer cell effector functions in antiviral defense

Abstract

Abbreviations: antibody-dependent cytotoxicity (ADCC); UA-rich elements (ARE); cyclic GMP-AMP synthase (cGAS); conserved non-coding sequence 1 (CNS1); DNAX accessory molecule 1 (DNAM-1); hepatitis B virus (HBV); hepatitis C virus (HCV); interferon (IFN); type I IFN (IFN-I); innate lymphoid cells (ILCs); interleukin (IL); killer cell immunoglobulin-like receptors (KIR); Accepted ArticleThis article is protected by copyright. All rights reserved lymphocyte-activation gene 3 (LAG-3); leukocyte immunoglobulin-like receptors (LILRs); murine cytomegalovirus (MCMV); major histocompatibility complex (MHC); MHC class I chain-related protein (MIC); murine UL16-binding protein-like transcript 1 (MULT1); natural cytotoxic receptor 1 (Ncr1); natural killer (NK); natural killer group 2D (NKG2D); programmed cell death 1 (PD-1); pattern recognition receptors (PRRs); poliovirus receptor (PVR); retinoic acid early inducible gene 1 (Rae-1); signaling lymphocytic activation molecule (SLAM); signal transducer and activator of transcription (STAT); stimulator of interferon gene (STING); T helper (Th); T cell immunoreceptor with Ig and ITIM domains (TIGIT); T-cell immunoglobulin mucin receptor 3 (TIM-3); TIR-domaincontaining adapter-inducing interferon-β (TRIF); toll like receptors (TLRs); UL16 binding protein (ULBP); untranslated region (UTR); vaccinia virus (VACV).

Human Hematopoietic Stem Cell Engrafted IL-15 Transgenic NSG Mice Support Robust NK Cell Responses and Sustained HIV-1 Infection

“…Along with T and B cells, NK cells are an essential antiviral weapon of the immune system. They respond quickly to infection, kill infected cells without prior activation, engage multiple targets simultaneously, and secrete large amounts of antiviral cytokines [ 9 , 10 ]. NK cells also mediate crosstalk with the adaptive immune system through antibody-dependent cell-mediated cytotoxicity (ADCC) [ 11 , 12 , 13 ].…”

The ectromelia virus virulence factor C15 facilitates early viral spread by inhibiting NK cell-infected cell contacts

“…NK cells can be activated by cytokines, which signal through the JAK-STAT pathway leading to IFNγ production and promoting cell replication. Separately, NK cells recognize target cells at contact points called immunological synapses by the integration of NK cell activating and inhibitory receptors through DAP-10/DAP-12 adaptors; this can trigger cytolysis, proliferation and IFNγ release via a mechanism more similar to T and B cell receptor signaling (Brandstadter and Yang, 2011; Piersma and Brizić, 2021). Therefore, while IFNγ production can be triggered by both cytokine-mediated activation and by target recognition, NK cell cytolytic degranulation occurs only following contact with a target cell resulting in formation of an activating immunologic synapse.…”

The ectromelia virus virulence factor C15 facilitates early viral spread by inhibiting NK cell contact

“…Separately, NK cells recognize target cells at contact points called immunological synapses by the integration of NK cell activating and inhibitory receptors through DAP-10/DAP-12 adaptors; this can trigger cytolysis, proliferation and IFNγ release via a mechanism more similar to T and B cell receptor signaling. 19 , 20 Therefore, while IFNγ production can be triggered by both cytokine-mediated activation and by target recognition, NK cell cytolytic degranulation occurs only following contact with a target cell resulting in formation of an activating immunologic synapse. Because we determined that C15 reduces the number of degranulating NK cells ( Figures 2 E and 4 A) but does not inhibit IFNγ ( Figures 2 E–2G and 4 A) or inhibit the transcripts for NK cell-activating cytokines ( Figures 3 F–3L), our data support a model in which C15 interferes with the target cell contact-dependent activation of NK cells.…”