After virus exposure, early bystander naïve CD8 T cell activation relies on NAD+ salvage metabolism

Frontiers in Immunology

Immunology

Gary Sisson¹  Steven P. Gygi²  Joao A. Paulo²  Christopher Richardson³  Prathyusha Konda⁴  Vishnupriyan Kumar⁵  Youra Kim⁵  Namit Holay⁵  Michael Giacomantonio⁵  J. Patrick Murphy⁶  Tatjana Brauer-Chapin⁷  Shashi Gujar⁸  Derek Clements⁹  Barry E. Kennedy^1,10  Mariam Elaghil^1,10 

[1] Department of Biology, University of Prince Edward Island, Charlottetown, PEI, Canada;Department of Cell Biology, Harvard Medical School, Harvard University, Boston, MA, United States;Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada;Canadian Centre for Vaccinology, IWK Health Centre, Goldbloom Pavilion, Halifax, NS, Canada;Department of Pediatrics, Dalhousie University, Halifax, NS, Canada;Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada;Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, United States;Department of Pathology, Dalhousie University, Halifax, NS, Canada;Department of Pathology, Dalhousie University, Halifax, NS, Canada;Department of Biology, University of Prince Edward Island, Charlottetown, PEI, Canada;Department of Pathology, Dalhousie University, Halifax, NS, Canada;Department of Cell Biology, Harvard Medical School, Harvard University, Boston, MA, United States;Department of Pathology, Dalhousie University, Halifax, NS, Canada;Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada;Department of Biology, Dalhousie University, Halifax, NS, Canada;Beatrice Hunter Cancer Research Institute, Halifax, NS, Canada;Cancer Immunotherapy: Innovation & Global Partnerships, Faculty of Medicine, Dalhousie University, Halifax, NS, Canada;Department of Pathology, Dalhousie University, Halifax, NS, Canada;Department of Microbiology and Immunology, Stanford University, Stanford, CA, United States;Department of Pathology, Dalhousie University, Halifax, NS, Canada;IMV Inc, Halifax, NS, Canada;

关键词: antiviral immunity;    CD8 T cells;    bystander activation;    naïve CD8 T cells;    type I interferons;    immunometabolism;    NAD salvage metabolism;    metabolic reprogramming;   

DOI  :  10.3389/fimmu.2022.1047661

 received in 2022-09-18, accepted in 2022-12-20,  发布年份 2023

来源: Frontiers

【 摘 要 】

CD8 T cells play a central role in antiviral immunity. Type I interferons are among the earliest responders after virus exposure and can cause extensive reprogramming and antigen-independent bystander activation of CD8 T cells. Although bystander activation of pre-existing memory CD8 T cells is known to play an important role in host defense and immunopathology, its impact on naïve CD8 T cells remains underappreciated. Here we report that exposure to reovirus, both in vitro or in vivo, promotes bystander activation of naïve CD8 T cells within 24 hours and that this distinct subtype of CD8 T cell displays an innate, antiviral, type I interferon sensitized signature. The induction of bystander naïve CD8 T cells is STAT1 dependent and regulated through nicotinamide phosphoribosyl transferase (NAMPT)-mediated enzymatic actions within NAD+ salvage metabolic biosynthesis. These findings identify a novel aspect of CD8 T cell activation following virus infection with implications for human health and physiology.

【 授权许可】

Unknown   
Copyright © 2023 Holay, Kennedy, Murphy, Konda, Giacomantonio, Brauer-Chapin, Paulo, Kumar, Kim, Elaghil, Sisson, Clements, Richardson, Gygi and Gujar