Increasing HbA1c is associated with reduced CD8 + T cell functionality in response to influenza virus in a TCR-dependent manner in individuals with diabetes mellitus.

Autor: Hulme KD; School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD, Australia.; Department of Medical Microbiology & Infection Prevention, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands., Tong ZWM; School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD, Australia., Rowntree LC; Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Parkville, VIC, Australia., van de Sandt CE; Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Parkville, VIC, Australia.; Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands., Ronacher K; Mater Research Institute, Translational Research Institute, The University of Queensland, Brisbane, Australia.; Australian Infectious Diseases Research Centre, The University of Queensland, St Lucia, QLD, Australia., Grant EJ; Department of Biochemistry and Chemistry, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC, Australia.; Department of Biochemistry and Molecular Biology and Infection and Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia., Dorey ES; Mater Research Institute, Translational Research Institute, The University of Queensland, Brisbane, Australia., Gallo LA; School of Biomedical Sciences, The University of Queensland, St Lucia, QLD, Australia.; School of Health and Behavioural Sciences, University of the Sunshine Coast, Moreton Bay, QLD, Australia., Gras S; Department of Biochemistry and Chemistry, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC, Australia.; Department of Biochemistry and Molecular Biology and Infection and Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia., Kedzierska K; Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Parkville, VIC, Australia., Barrett HL; Mater Research Institute, Translational Research Institute, The University of Queensland, Brisbane, Australia.; Obstetric Medicine, The Royal Hospital for Women, Randwick, NSW, Australia.; School of Medicine, UNSW, Randwick, NSW, Australia., Short KR; School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD, Australia. k.short@uq.edu.au.; Australian Infectious Diseases Research Centre, The University of Queensland, St Lucia, QLD, Australia. k.short@uq.edu.au.
Jazyk: angličtina
Zdroj: Cellular and molecular life sciences : CMLS [Cell Mol Life Sci] 2024 Jan 12; Vol. 81 (1), pp. 35. Date of Electronic Publication: 2024 Jan 12.
DOI: 10.1007/s00018-023-05010-4
Abstrakt: Diabetes mellitus is on the rise globally and is a known susceptibility factor for severe influenza virus infections. However, the mechanisms by which diabetes increases the severity of an influenza virus infection are yet to be fully defined. Diabetes mellitus is hallmarked by high glucose concentrations in the blood. We hypothesized that these high glucose concentrations affect the functionality of CD8 + T cells, which play a key role eliminating virus-infected cells and have been shown to decrease influenza disease severity. To study the effect of hyperglycemia on CD8 + T cell function, we stimulated peripheral blood mononuclear cells (PBMCs) from donors with and without diabetes with influenza A virus, anti-CD3/anti-CD28-coated beads, PMA and ionomycin (PMA/I), or an influenza viral peptide pool. After stimulation, cells were assessed for functionality [as defined by expression of IFN-γ, TNF-α, macrophage inflammatory protein (MIP)-1β, and lysosomal-associated membrane protein-1 (CD107a)] using flow cytometry. Our results showed that increasing HbA1c correlated with a reduction in TNF-α production by CD8 + T cells in response to influenza stimulation in a TCR-specific manner. This was not associated with any changes to CD8 + T cell subsets. We conclude that hyperglycemia impairs CD8 + T cell function to influenza virus infection, which may be linked with the increased risk of severe influenza in patients with diabetes.
(© 2024. The Author(s).)
Databáze: MEDLINE
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