Frontiers in Immunology (Feb 2023)
After virus exposure, early bystander naïve CD8 T cell activation relies on NAD+ salvage metabolism
- Namit Holay,
- Barry E. Kennedy,
- Barry E. Kennedy,
- J. Patrick Murphy,
- J. Patrick Murphy,
- Prathyusha Konda,
- Prathyusha Konda,
- Michael Giacomantonio,
- Tatjana Brauer-Chapin,
- Tatjana Brauer-Chapin,
- Joao A. Paulo,
- Vishnupriyan Kumar,
- Youra Kim,
- Mariam Elaghil,
- Mariam Elaghil,
- Gary Sisson,
- Derek Clements,
- Derek Clements,
- Christopher Richardson,
- Christopher Richardson,
- Christopher Richardson,
- Steven P. Gygi,
- Shashi Gujar,
- Shashi Gujar,
- Shashi Gujar,
- Shashi Gujar,
- Shashi Gujar
Affiliations
- Namit Holay
- Department of Pathology, Dalhousie University, Halifax, NS, Canada
- Barry E. Kennedy
- Department of Pathology, Dalhousie University, Halifax, NS, Canada
- Barry E. Kennedy
- IMV Inc, Halifax, NS, Canada
- J. Patrick Murphy
- Department of Pathology, Dalhousie University, Halifax, NS, Canada
- J. Patrick Murphy
- Department of Biology, University of Prince Edward Island, Charlottetown, PEI, Canada
- Prathyusha Konda
- Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada
- Prathyusha Konda
- Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, United States
- Michael Giacomantonio
- Department of Pathology, Dalhousie University, Halifax, NS, Canada
- Tatjana Brauer-Chapin
- Department of Pathology, Dalhousie University, Halifax, NS, Canada
- Tatjana Brauer-Chapin
- Department of Cell Biology, Harvard Medical School, Harvard University, Boston, MA, United States
- Joao A. Paulo
- Department of Cell Biology, Harvard Medical School, Harvard University, Boston, MA, United States
- Vishnupriyan Kumar
- Department of Pathology, Dalhousie University, Halifax, NS, Canada
- Youra Kim
- Department of Pathology, Dalhousie University, Halifax, NS, Canada
- Mariam Elaghil
- Department of Pathology, Dalhousie University, Halifax, NS, Canada
- Mariam Elaghil
- IMV Inc, Halifax, NS, Canada
- Gary Sisson
- Department of Biology, University of Prince Edward Island, Charlottetown, PEI, Canada
- Derek Clements
- Department of Pathology, Dalhousie University, Halifax, NS, Canada
- Derek Clements
- Department of Microbiology and Immunology, Stanford University, Stanford, CA, United States
- Christopher Richardson
- Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada
- Christopher Richardson
- Canadian Centre for Vaccinology, IWK Health Centre, Goldbloom Pavilion, Halifax, NS, Canada
- Christopher Richardson
- 0Department of Pediatrics, Dalhousie University, Halifax, NS, Canada
- Steven P. Gygi
- Department of Cell Biology, Harvard Medical School, Harvard University, Boston, MA, United States
- Shashi Gujar
- Department of Pathology, Dalhousie University, Halifax, NS, Canada
- Shashi Gujar
- Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada
- Shashi Gujar
- 1Department of Biology, Dalhousie University, Halifax, NS, Canada
- Shashi Gujar
- 2Beatrice Hunter Cancer Research Institute, Halifax, NS, Canada
- Shashi Gujar
- 3Cancer Immunotherapy: Innovation & Global Partnerships, Faculty of Medicine, Dalhousie University, Halifax, NS, Canada
- DOI
- https://doi.org/10.3389/fimmu.2022.1047661
- Journal volume & issue
-
Vol. 13
Abstract
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.
Keywords
- antiviral immunity
- CD8 T cells
- bystander activation
- naïve CD8 T cells
- type I interferons
- immunometabolism
