Cargando…

Baseline T cell immune phenotypes predict virologic and disease control upon SARS-CoV infection in Collaborative Cross mice

The COVID-19 pandemic has revealed that infection with SARS-CoV-2 can result in a wide range of clinical outcomes in humans. An incomplete understanding of immune correlates of protection represents a major barrier to the design of vaccines and therapeutic approaches to prevent infection or limit di...

Descripción completa

Detalles Bibliográficos
Autores principales: Graham, Jessica B., Swarts, Jessica L., Leist, Sarah R., Schäfer, Alexandra, Menachery, Vineet D., Gralinski, Lisa E., Jeng, Sophia, Miller, Darla R., Mooney, Michael A., McWeeney, Shannon K., Ferris, Martin T., Pardo-Manuel de Villena, Fernando, Heise, Mark T., Baric, Ralph S., Lund, Jennifer M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875398/
https://www.ncbi.nlm.nih.gov/pubmed/33513210
http://dx.doi.org/10.1371/journal.ppat.1009287
_version_ 1783649765425152000
author Graham, Jessica B.
Swarts, Jessica L.
Leist, Sarah R.
Schäfer, Alexandra
Menachery, Vineet D.
Gralinski, Lisa E.
Jeng, Sophia
Miller, Darla R.
Mooney, Michael A.
McWeeney, Shannon K.
Ferris, Martin T.
Pardo-Manuel de Villena, Fernando
Heise, Mark T.
Baric, Ralph S.
Lund, Jennifer M.
author_facet Graham, Jessica B.
Swarts, Jessica L.
Leist, Sarah R.
Schäfer, Alexandra
Menachery, Vineet D.
Gralinski, Lisa E.
Jeng, Sophia
Miller, Darla R.
Mooney, Michael A.
McWeeney, Shannon K.
Ferris, Martin T.
Pardo-Manuel de Villena, Fernando
Heise, Mark T.
Baric, Ralph S.
Lund, Jennifer M.
author_sort Graham, Jessica B.
collection PubMed
description The COVID-19 pandemic has revealed that infection with SARS-CoV-2 can result in a wide range of clinical outcomes in humans. An incomplete understanding of immune correlates of protection represents a major barrier to the design of vaccines and therapeutic approaches to prevent infection or limit disease. This deficit is largely due to the lack of prospectively collected, pre-infection samples from individuals that go on to become infected with SARS-CoV-2. Here, we utilized data from genetically diverse Collaborative Cross (CC) mice infected with SARS-CoV to determine whether baseline T cell signatures are associated with a lack of viral control and severe disease upon infection. SARS-CoV infection of CC mice results in a variety of viral load trajectories and disease outcomes. Overall, a dysregulated, pro-inflammatory signature of circulating T cells at baseline was associated with severe disease upon infection. Our study serves as proof of concept that circulating T cell signatures at baseline can predict clinical and virologic outcomes upon SARS-CoV infection. Identification of basal immune predictors in humans could allow for identification of individuals at highest risk of severe clinical and virologic outcomes upon infection, who may thus most benefit from available clinical interventions to restrict infection and disease.
format Online
Article
Text
id pubmed-7875398
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-78753982021-02-19 Baseline T cell immune phenotypes predict virologic and disease control upon SARS-CoV infection in Collaborative Cross mice Graham, Jessica B. Swarts, Jessica L. Leist, Sarah R. Schäfer, Alexandra Menachery, Vineet D. Gralinski, Lisa E. Jeng, Sophia Miller, Darla R. Mooney, Michael A. McWeeney, Shannon K. Ferris, Martin T. Pardo-Manuel de Villena, Fernando Heise, Mark T. Baric, Ralph S. Lund, Jennifer M. PLoS Pathog Research Article The COVID-19 pandemic has revealed that infection with SARS-CoV-2 can result in a wide range of clinical outcomes in humans. An incomplete understanding of immune correlates of protection represents a major barrier to the design of vaccines and therapeutic approaches to prevent infection or limit disease. This deficit is largely due to the lack of prospectively collected, pre-infection samples from individuals that go on to become infected with SARS-CoV-2. Here, we utilized data from genetically diverse Collaborative Cross (CC) mice infected with SARS-CoV to determine whether baseline T cell signatures are associated with a lack of viral control and severe disease upon infection. SARS-CoV infection of CC mice results in a variety of viral load trajectories and disease outcomes. Overall, a dysregulated, pro-inflammatory signature of circulating T cells at baseline was associated with severe disease upon infection. Our study serves as proof of concept that circulating T cell signatures at baseline can predict clinical and virologic outcomes upon SARS-CoV infection. Identification of basal immune predictors in humans could allow for identification of individuals at highest risk of severe clinical and virologic outcomes upon infection, who may thus most benefit from available clinical interventions to restrict infection and disease. Public Library of Science 2021-01-29 /pmc/articles/PMC7875398/ /pubmed/33513210 http://dx.doi.org/10.1371/journal.ppat.1009287 Text en © 2021 Graham et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Graham, Jessica B.
Swarts, Jessica L.
Leist, Sarah R.
Schäfer, Alexandra
Menachery, Vineet D.
Gralinski, Lisa E.
Jeng, Sophia
Miller, Darla R.
Mooney, Michael A.
McWeeney, Shannon K.
Ferris, Martin T.
Pardo-Manuel de Villena, Fernando
Heise, Mark T.
Baric, Ralph S.
Lund, Jennifer M.
Baseline T cell immune phenotypes predict virologic and disease control upon SARS-CoV infection in Collaborative Cross mice
title Baseline T cell immune phenotypes predict virologic and disease control upon SARS-CoV infection in Collaborative Cross mice
title_full Baseline T cell immune phenotypes predict virologic and disease control upon SARS-CoV infection in Collaborative Cross mice
title_fullStr Baseline T cell immune phenotypes predict virologic and disease control upon SARS-CoV infection in Collaborative Cross mice
title_full_unstemmed Baseline T cell immune phenotypes predict virologic and disease control upon SARS-CoV infection in Collaborative Cross mice
title_short Baseline T cell immune phenotypes predict virologic and disease control upon SARS-CoV infection in Collaborative Cross mice
title_sort baseline t cell immune phenotypes predict virologic and disease control upon sars-cov infection in collaborative cross mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875398/
https://www.ncbi.nlm.nih.gov/pubmed/33513210
http://dx.doi.org/10.1371/journal.ppat.1009287
work_keys_str_mv AT grahamjessicab baselinetcellimmunephenotypespredictvirologicanddiseasecontroluponsarscovinfectionincollaborativecrossmice
AT swartsjessical baselinetcellimmunephenotypespredictvirologicanddiseasecontroluponsarscovinfectionincollaborativecrossmice
AT leistsarahr baselinetcellimmunephenotypespredictvirologicanddiseasecontroluponsarscovinfectionincollaborativecrossmice
AT schaferalexandra baselinetcellimmunephenotypespredictvirologicanddiseasecontroluponsarscovinfectionincollaborativecrossmice
AT menacheryvineetd baselinetcellimmunephenotypespredictvirologicanddiseasecontroluponsarscovinfectionincollaborativecrossmice
AT gralinskilisae baselinetcellimmunephenotypespredictvirologicanddiseasecontroluponsarscovinfectionincollaborativecrossmice
AT jengsophia baselinetcellimmunephenotypespredictvirologicanddiseasecontroluponsarscovinfectionincollaborativecrossmice
AT millerdarlar baselinetcellimmunephenotypespredictvirologicanddiseasecontroluponsarscovinfectionincollaborativecrossmice
AT mooneymichaela baselinetcellimmunephenotypespredictvirologicanddiseasecontroluponsarscovinfectionincollaborativecrossmice
AT mcweeneyshannonk baselinetcellimmunephenotypespredictvirologicanddiseasecontroluponsarscovinfectionincollaborativecrossmice
AT ferrismartint baselinetcellimmunephenotypespredictvirologicanddiseasecontroluponsarscovinfectionincollaborativecrossmice
AT pardomanueldevillenafernando baselinetcellimmunephenotypespredictvirologicanddiseasecontroluponsarscovinfectionincollaborativecrossmice
AT heisemarkt baselinetcellimmunephenotypespredictvirologicanddiseasecontroluponsarscovinfectionincollaborativecrossmice
AT baricralphs baselinetcellimmunephenotypespredictvirologicanddiseasecontroluponsarscovinfectionincollaborativecrossmice
AT lundjenniferm baselinetcellimmunephenotypespredictvirologicanddiseasecontroluponsarscovinfectionincollaborativecrossmice