Files and links (1)
Published VersionCC BY V4.0, Open Access
Journal article
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
Cellular and Molecular Life Sciences, Vol.81, pp.1-11
2024
PMID: 38214784
Abstract
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.
Details
- Title
- 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
- Authors
- Katina D Hulme (Author) - The University of QueenslandZhen Wei Marcus Tong (Author) - The University of QueenslandLouise C Rowntree (Author) - Peter Doherty InstituteCarolien E van de Sandt (Author) - Peter Doherty InstituteKatharina Ronacher (Author) - The University of QueenslandEmma J Grant (Author) - La Trobe UniversityEmily S Dorey (Author) - Mater ResearchLinda A Gallo (Author) - University of the Sunshine Coast, Queensland, School of Health - BiomedicineStephanie Gras (Author) - La Trobe UniversityKatherine Kedzierska (Author) - Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Parkville, VIC, AustraliaHelen L Barrett (Author) - Mater Health ServicesKirsty R Short (Corresponding Author) - The University of Queensland
- Publication details
- Cellular and Molecular Life Sciences, Vol.81, pp.1-11
- Publisher
- Birkhaeuser Science
- Date published
- 2024
- DOI
- 10.1007/s00018-023-05010-4
- ISSN
- 1420-9071; 1420-682X
- PMID
- 38214784
- Copyright note
- This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
- Data Availability
- The data sets generated during the current study are not publicly available due to nature of the ethical approvals. If you have a reasonable request, please contact the corresponding author.
- Organisation Unit
- School of Health - Biomedicine
- Language
- English
- Record Identifier
- 99999998602621
- Output Type
- Journal article
Metrics
47 Record Views
InCites Highlights
These are selected metrics from InCites Benchmarking & Analytics tool, related to this output
- Collaboration types
- Domestic collaboration
- International collaboration
- Web Of Science research areas
- Biochemistry & Molecular Biology
- Cell Biology
UN Sustainable Development Goals (SDGs)
This output has contributed to the advancement of the following goals:
Source: InCites