Short, C.-E. | Search bioRxiv

bioRxiv2025

Accelerated memory T cell decline and tolerogenic recall responses to SARS-CoV-2 vaccination in diabetes

Type 1 and type 2 diabetes are associated with increased severity and mortality from respiratory virus infections, including SARS-CoV-2. Vaccination in the general population significantly reduces the risk of severe respiratory viral infection and triggers a strong, polyfunctional and lasting T cell response in healthy individuals. However, vaccine effectiveness in people with diabetes is unclear. Here we studied the magnitude and functional characteristics of vaccine-specific CD4+ and CD8+ T cell responses to the full vaccination protocol, and the recall response after a third booster dose of SARS-CoV-2 vaccine in people with type 1 and type 2 diabetes, and compared them to those of people without diabetes. We found defects in both CD4+ and CD8+ T cell memory maintenance and the functionality of the vaccine specific T cells in people with diabetes compared to people without. In those individuals with diabetes that harbored detectable vaccine-specific T cells, they displayed an unfocused, tolerogenic phenotype characterized by increased expression of IL-13 and IL-10 in T1D and T2D compared to people without diabetes. These results have implications for vaccination strategies for people with diabetes.

immunology↗

bioRxiv2022

Transcriptional reprogramming from innate immune functions to a pro-thrombotic signature upon SARS-CoV-2 sensing by monocytes in COVID-19

Alterations in the myeloid immune compartment have been observed in COVID-19, but the specific mechanisms underlying these impairments are not completely understood. Here we examined the functionality of classical CD14+ monocytes as a main myeloid cell component in well-defined cohorts of patients with mild and moderate COVID-19 during the acute phase of infection and compared them to that of healthy individuals. We found that ex vivo isolated CD14+ monocytes from mild and moderate COVID-19 patients display specific patterns of costimulatory and inhibitory receptors that clearly distinguish them from healthy monocytes, as well as altered expression of histone marks and a dysfunctional metabolic profile. Decreased NF{kappa}B activation in COVID-19 monocytes ex vivo is accompanied by an intact type I IFN antiviral response. Subsequent pathogen sensing ex vivo led to a state of functional unresponsiveness characterized by a defect in pro-inflammatory cytokine expression, NF{kappa}B-driven cytokine responses and defective type I IFN response in moderate COVID-19 monocytes. Transcriptionally, COVID-19 monocytes switched their gene expression signature from canonical innate immune functions to a pro-thrombotic phenotype characterized by increased expression of pathways involved in hemostasis and immunothrombosis. In response to SARS-CoV-2 or other viral or bacterial components, monocytes displayed defects in the epigenetic remodelling and metabolic reprogramming that usually occurs upon pathogen sensing in innate immune cells. These results provide a potential mechanism by which innate immune dysfunction in COVID-19 may contribute to disease pathology.

immunology↗