After virus exposure, early bystander naïve CD8 T cell activation relies on NAD+ salvage metabolism
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 know...
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-02-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1047661/full |
| _version_ | 1828047401709993984 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Namit Holay |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-10T18:40:31Z |
| format | Article |
| id | doaj.art-43247c5da956443a994817e22e2a9b5e |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-10T18:40:31Z |
| publishDate | 2023-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-43247c5da956443a994817e22e2a9b5e2023-02-01T15:00:32ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-02-011310.3389/fimmu.2022.10476611047661After virus exposure, early bystander naïve CD8 T cell activation relies on NAD+ salvage metabolismNamit Holay0Barry E. Kennedy1Barry E. Kennedy2J. Patrick Murphy3J. Patrick Murphy4Prathyusha Konda5Prathyusha Konda6Michael Giacomantonio7Tatjana Brauer-Chapin8Tatjana Brauer-Chapin9Joao A. Paulo10Vishnupriyan Kumar11Youra Kim12Mariam Elaghil13Mariam Elaghil14Gary Sisson15Derek Clements16Derek Clements17Christopher Richardson18Christopher Richardson19Christopher Richardson20Steven P. Gygi21Shashi Gujar22Shashi Gujar23Shashi Gujar24Shashi Gujar25Shashi Gujar26Department of Pathology, Dalhousie University, Halifax, NS, CanadaDepartment of Pathology, Dalhousie University, Halifax, NS, CanadaIMV Inc, Halifax, NS, CanadaDepartment of Pathology, Dalhousie University, Halifax, NS, CanadaDepartment of Biology, University of Prince Edward Island, Charlottetown, PEI, CanadaDepartment of Microbiology and Immunology, Dalhousie University, Halifax, NS, CanadaDana Farber Cancer Institute, Harvard Medical School, Boston, MA, United StatesDepartment of Pathology, Dalhousie University, Halifax, NS, CanadaDepartment of Pathology, Dalhousie University, Halifax, NS, CanadaDepartment of Cell Biology, Harvard Medical School, Harvard University, Boston, MA, United StatesDepartment of Cell Biology, Harvard Medical School, Harvard University, Boston, MA, United StatesDepartment of Pathology, Dalhousie University, Halifax, NS, CanadaDepartment of Pathology, Dalhousie University, Halifax, NS, CanadaDepartment of Pathology, Dalhousie University, Halifax, NS, CanadaIMV Inc, Halifax, NS, CanadaDepartment of Biology, University of Prince Edward Island, Charlottetown, PEI, CanadaDepartment of Pathology, Dalhousie University, Halifax, NS, CanadaDepartment of Microbiology and Immunology, Stanford University, Stanford, CA, United StatesDepartment of Microbiology and Immunology, Dalhousie University, Halifax, NS, CanadaCanadian Centre for Vaccinology, IWK Health Centre, Goldbloom Pavilion, Halifax, NS, Canada0Department of Pediatrics, Dalhousie University, Halifax, NS, CanadaDepartment of Cell Biology, Harvard Medical School, Harvard University, Boston, MA, United StatesDepartment of Pathology, Dalhousie University, Halifax, NS, CanadaDepartment of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada1Department of Biology, Dalhousie University, Halifax, NS, Canada2Beatrice Hunter Cancer Research Institute, Halifax, NS, Canada3Cancer Immunotherapy: Innovation & Global Partnerships, Faculty of Medicine, Dalhousie University, Halifax, NS, CanadaCD8 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.https://www.frontiersin.org/articles/10.3389/fimmu.2022.1047661/fullantiviral immunityCD8 T cellsbystander activationnaïve CD8 T cellstype I interferonsimmunometabolism |
| spellingShingle | 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 After virus exposure, early bystander naïve CD8 T cell activation relies on NAD+ salvage metabolism Frontiers in Immunology antiviral immunity CD8 T cells bystander activation naïve CD8 T cells type I interferons immunometabolism |
| title | After virus exposure, early bystander naïve CD8 T cell activation relies on NAD+ salvage metabolism |
| title_full | After virus exposure, early bystander naïve CD8 T cell activation relies on NAD+ salvage metabolism |
| title_fullStr | After virus exposure, early bystander naïve CD8 T cell activation relies on NAD+ salvage metabolism |
| title_full_unstemmed | After virus exposure, early bystander naïve CD8 T cell activation relies on NAD+ salvage metabolism |
| title_short | After virus exposure, early bystander naïve CD8 T cell activation relies on NAD+ salvage metabolism |
| title_sort | after virus exposure early bystander naive cd8 t cell activation relies on nad salvage metabolism |
| topic | antiviral immunity CD8 T cells bystander activation naïve CD8 T cells type I interferons immunometabolism |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1047661/full |
| work_keys_str_mv | AT namitholay aftervirusexposureearlybystandernaivecd8tcellactivationreliesonnadsalvagemetabolism AT barryekennedy aftervirusexposureearlybystandernaivecd8tcellactivationreliesonnadsalvagemetabolism AT barryekennedy aftervirusexposureearlybystandernaivecd8tcellactivationreliesonnadsalvagemetabolism AT jpatrickmurphy aftervirusexposureearlybystandernaivecd8tcellactivationreliesonnadsalvagemetabolism AT jpatrickmurphy aftervirusexposureearlybystandernaivecd8tcellactivationreliesonnadsalvagemetabolism AT prathyushakonda aftervirusexposureearlybystandernaivecd8tcellactivationreliesonnadsalvagemetabolism AT prathyushakonda aftervirusexposureearlybystandernaivecd8tcellactivationreliesonnadsalvagemetabolism AT michaelgiacomantonio aftervirusexposureearlybystandernaivecd8tcellactivationreliesonnadsalvagemetabolism AT tatjanabrauerchapin aftervirusexposureearlybystandernaivecd8tcellactivationreliesonnadsalvagemetabolism AT tatjanabrauerchapin aftervirusexposureearlybystandernaivecd8tcellactivationreliesonnadsalvagemetabolism AT joaoapaulo aftervirusexposureearlybystandernaivecd8tcellactivationreliesonnadsalvagemetabolism AT vishnupriyankumar aftervirusexposureearlybystandernaivecd8tcellactivationreliesonnadsalvagemetabolism AT yourakim aftervirusexposureearlybystandernaivecd8tcellactivationreliesonnadsalvagemetabolism AT mariamelaghil aftervirusexposureearlybystandernaivecd8tcellactivationreliesonnadsalvagemetabolism AT mariamelaghil aftervirusexposureearlybystandernaivecd8tcellactivationreliesonnadsalvagemetabolism AT garysisson aftervirusexposureearlybystandernaivecd8tcellactivationreliesonnadsalvagemetabolism AT derekclements aftervirusexposureearlybystandernaivecd8tcellactivationreliesonnadsalvagemetabolism AT derekclements aftervirusexposureearlybystandernaivecd8tcellactivationreliesonnadsalvagemetabolism AT christopherrichardson aftervirusexposureearlybystandernaivecd8tcellactivationreliesonnadsalvagemetabolism AT christopherrichardson aftervirusexposureearlybystandernaivecd8tcellactivationreliesonnadsalvagemetabolism AT christopherrichardson aftervirusexposureearlybystandernaivecd8tcellactivationreliesonnadsalvagemetabolism AT stevenpgygi aftervirusexposureearlybystandernaivecd8tcellactivationreliesonnadsalvagemetabolism AT shashigujar aftervirusexposureearlybystandernaivecd8tcellactivationreliesonnadsalvagemetabolism AT shashigujar aftervirusexposureearlybystandernaivecd8tcellactivationreliesonnadsalvagemetabolism AT shashigujar aftervirusexposureearlybystandernaivecd8tcellactivationreliesonnadsalvagemetabolism AT shashigujar aftervirusexposureearlybystandernaivecd8tcellactivationreliesonnadsalvagemetabolism AT shashigujar aftervirusexposureearlybystandernaivecd8tcellactivationreliesonnadsalvagemetabolism |