High glycemic variability is associated with a reduced T cell cytokine response to influenza A virus

Marcus Z W Tong; Katina D Hulme; Soi Cheng Law; Ellesandra Noye; Emily S Dorey; Keng Yih Chew; Louise C Rowntree; Carolien E van de Sandt; Katherine Kedzierska; Marco Goeijenbier; Katharina Ronacher; Fawaz Alzaid; Jean-Baptiste Julla; Jean-Pierre Riveline; Katie E Lineburg; Corey Smith; Emma J Grant; Stephanie Gras; Linda A Gallo; Helen L Barrett; Kirsty R Short

doi:10.1016/j.isci.2024.111166

High glycemic variability is associated with a reduced T cell cytokine response to influenza A virus

iScience. 2024 Oct 11;27(11):111166. doi: 10.1016/j.isci.2024.111166. eCollection 2024 Nov 15.

Authors

Marcus Z W Tong¹, Katina D Hulme^{1

2}, Soi Cheng Law³, Ellesandra Noye¹, Emily S Dorey³, Keng Yih Chew¹, Louise C Rowntree⁴, Carolien E van de Sandt^{4

5}, Katherine Kedzierska⁴, Marco Goeijenbier^{6

7}, Katharina Ronacher^{3

8}, Fawaz Alzaid^{9

10}, Jean-Baptiste Julla^{9

11}, Jean-Pierre Riveline^{9

11}, Katie E Lineburg¹², Corey Smith^{12

13}, Emma J Grant^{14

15}, Stephanie Gras^{14

15}, Linda A Gallo¹⁶, Helen L Barrett^{3

17

18}, Kirsty R Short^{1

8

13}

Affiliations

¹ School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD, Australia.
² Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
³ Mater Research Institute, The University of Queensland, Translational Research Institute, Brisbane, QLD, Australia.
⁴ Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
⁵ Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
⁶ Department of Intensive Care, Erasmus MC, Rotterdam, the Netherlands.
⁷ Department of Intensive Care, Spaarne Gasthuis, Haarlem, Hoofddorp, the Netherlands.
⁸ Australian Infectious Diseases Research Centre, The University of Queensland, St Lucia, QLD, Australia.
⁹ Université Paris Cité, CNRS, INSERM, Institut Necker Enfants Malades-INEM, F-75015 Paris, France.
¹⁰ Dasman Diabetes Institute, Kuwait, Kuwait.
¹¹ Department of Diabetes, Clinical Investigation Centre (CIC-9504), Lariboisière Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France.
¹² QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
¹³ Queensland Immunology Research Centre, St Lucia, QLD, Australia.
¹⁴ Department of Biochemistry and Chemistry, La Trobe Institute for Molecular Science, Bundoora, VIC, Australia.
¹⁵ Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Clayton, VIC, Australia.
¹⁶ School of Health and Behavioural Sciences, University of the Sunshine Coast, Petrie, QLD, Australia.
¹⁷ University of New South Wales Medicine, Kensington, NSW, Australia.
¹⁸ Obstetric Medicine, Royal Hospital for Women, Randwick, NSW, Australia.

Abstract

Diabetes mellitus significantly increases the risk of severe respiratory virus disease like influenza and COVID-19. Early evidence suggests that this susceptibility to respiratory viral disease is driven by glycemic variability, rather than average blood glucose levels. Here, we use blood samples and constant glucose monitoring (CGM) data obtained from people living with type 1 diabetes (T1D) to determine the effects of glycemic variability on the ex vivo T cell response to influenza virus. We show that high glycemic variability in participants living with T1D is associated with a reduced proportion of CD8⁺CD107a^-IFNγ^-MIP1β^-TNF⁺ T cells in response to stimulation with influenza virus and an influenza virus peptide pool. Thus, this study provides evidence that glycemic variability affects the ex vivo T cell response to respiratory viruses. These data suggest that monitoring glycemic variability may have important implications in understanding the antiviral immune response in people with diabetes.

Keywords: Endocrinology; Human metabolism.