Extracellular vesicles in COVID-19 convalescence can regulate T cell metabolism and function

TY - JOUR

T1 - Extracellular vesicles in COVID-19 convalescence can regulate T cell metabolism and function

AU - George, Molly s.

AU - Sanchez, Jenifer

AU - Rollings, Christina

AU - Fear, David

AU - Irving, Peter

AU - Sinclair, Linda v.

AU - Schurich, Anna

N1 - Funding Information: We thank Prof Doreen Cantrell and colleagues at the University of Dundee for generous support with proteomics. We would like to thank Stefan Wild, Laura Mara Müller, and Ute Heider at Miltenyi Biotec for technical support and scientific discussion. We would like to thank Kate Brooks at KCL for support with donor recruitment. We would like to acknowledge support from Christine Mant at the Infectious Diseases Biobank at KCL , funded by the NIHR Biomedical Research Centre facility and the Guy’s & St Thomas’ Charity. We sincerely thank all blood donors for supporting our research. We thank Rafael Argüello at INSERM for helpful discussion of the SCENITH technique, https://www.scenith.com/ . This work was financially supported by: KMRT Studentships to A. Schurich, M. George; British Society for Antimicrobial Chemotherapy ( BSAC-COVID-07 ) grant to A. Schurich and P. Irving; King’s Together Rapid Covid Call to D. Fear. Proteomics work was funded by the Chief Scientist Office Rapid Response COVID19 Research Grant ( COV/DUND/20/01 & COV/DUN/20/04 ) and the UK Coronavirus Immunology Consortium ( MR/V028448 ) and the Wellcome Trust ( 205023/Z/16/Z ). C. Rollings and L. Sinclair are supported by a Wellcome Trust Principal Research fellowship ( 097418/Z/11/Z ) to D. Cantrell. Funding Information: We thank Prof Doreen Cantrell and colleagues at the University of Dundee for generous support with proteomics. We would like to thank Stefan Wild, Laura Mara Müller, and Ute Heider at Miltenyi Biotec for technical support and scientific discussion. We would like to thank Kate Brooks at KCL for support with donor recruitment. We would like to acknowledge support from Christine Mant at the Infectious Diseases Biobank at KCL, funded by the NIHR Biomedical Research Centre facility and the Guy's & St Thomas’ Charity. We sincerely thank all blood donors for supporting our research. We thank Rafael Argüello at INSERM for helpful discussion of the SCENITH technique, https://www.scenith.com/. This work was financially supported by: KMRT Studentships to A. Schurich, M. George; British Society for Antimicrobial Chemotherapy (BSAC-COVID-07) grant to A. Schurich and P. Irving; King's Together Rapid Covid Call to D. Fear. Proteomics work was funded by the Chief Scientist Office Rapid Response COVID19 Research Grant (COV/DUND/20/01 & COV/DUN/20/04) and the UK Coronavirus Immunology Consortium (MR/V028448) and the Wellcome Trust (205023/Z/16/Z). C. Rollings and L. Sinclair are supported by a Wellcome Trust Principal Research fellowship (097418/Z/11/Z) to D. Cantrell. Conceptualization, A.S.; experimental design, M.G. J.S. L.S. and A.S.; experimental work and data analysis, M.G. J.S. and C.R.; figure preparation M.G. and J.S.; sample acquisition, D.F. A.S.; funding acquisition, L.S. D.F. P.I. and A.S. data discussion, all authors; writing-original draft, M.G. and A.S.; writing-review and editing, all authors. The authors declare no competing interests. We support inclusive, diverse, and equitable conduct of research. Publisher Copyright: © 2023 The Authors

PY - 2023/8/18

Y1 - 2023/8/18

N2 - Long-term T cell dysregulation has been reported following COVID-19 disease. Prolonged T cell activation is associated with disease severity and may be implicated in producing long-covid symptoms. Here, we assess the role of extracellular vesicles (EV) in regulating T cell function over several weeks post COVID-19 disease. We find that alterations in cellular origin and protein content of EV in COVID-19 convalescence are linked to initial disease severity. We demonstrate that convalescent donor-derived EV can alter the function and metabolic rewiring of CD4 and CD8 T cells. Of note, EV following mild, but not severe disease, show distinctly immune-suppressive properties, reducing T cell effector cytokine production and glucose metabolism. Mechanistically our data indicate the involvement of EV-surface ICAM-1 in facilitating EV—T cell interaction. Our data demonstrate that circulatory EV are phenotypically and functionally altered several weeks following acute infection, suggesting a role for EV as long-term immune modulators.

AB - Long-term T cell dysregulation has been reported following COVID-19 disease. Prolonged T cell activation is associated with disease severity and may be implicated in producing long-covid symptoms. Here, we assess the role of extracellular vesicles (EV) in regulating T cell function over several weeks post COVID-19 disease. We find that alterations in cellular origin and protein content of EV in COVID-19 convalescence are linked to initial disease severity. We demonstrate that convalescent donor-derived EV can alter the function and metabolic rewiring of CD4 and CD8 T cells. Of note, EV following mild, but not severe disease, show distinctly immune-suppressive properties, reducing T cell effector cytokine production and glucose metabolism. Mechanistically our data indicate the involvement of EV-surface ICAM-1 in facilitating EV—T cell interaction. Our data demonstrate that circulatory EV are phenotypically and functionally altered several weeks following acute infection, suggesting a role for EV as long-term immune modulators.

UR - http://www.scopus.com/inward/record.url?scp=85165084306&partnerID=8YFLogxK

U2 - 10.1016/j.isci.2023.107280

DO - 10.1016/j.isci.2023.107280

M3 - Article

SN - 2589-0042

VL - 26

JO - iScience

JF - iScience

IS - 8

M1 - 107280

ER -