Dengue and COVID-19 represent two major global health concerns. However, we still lack a complete understanding of the mechanisms underlying the role of adaptive immune cell responses. Here we investigated the role of T, NK, and B cells in two independent patient cohorts of patients with acute dengue and post-acute and convalescent COVID-19 individuals. We analysed patient samples using flow cytometry-based approaches to study the phenotype and functional characteristics of T, NK, and B cells, with a specific focus on T cell responses and their associations with disease severity and for dengue samples also obesity. We observed altered immune cell phenotypes in severe dengue patients, including increased plasmablasts and decreased cytotoxic potential of T and NK cells, which were strongly correlated with plasma leakage and markers related to dengue severity. Moreover, we found continuous increased PD-1 expression in CD4+ and CD8+ T cells from severe dengue patients as well as increased levels of multiple co-inhibitory receptors (e.g. LAG-3 and TIM-3), suggesting potential T cell exhaustion. PD-1/PD-L1 blockade resulted in enhanced cytotoxic capacity of CD8+ T cells. In convalescent COVID-19 patients, we observed increased T cell activation in severe patients at 3 months post infection, indicating persistent inflammation. In addition, we detected an increased frequency of CD4+ T cells specific to unrelated antigen, suggesting bystander activation in COVID-19 patients. Collectively, we found alterations in T, NK, and B cell phenotypes and/or functional properties of severe acute dengue and COVID-19 patients. Moreover, our findings suggest potential exhaustion/impairment in the T cell response in severe dengue, which was partially restored by PD-1/PD-L1 blockade. Understanding the mechanisms underlying T cell dysfunction in severe dengue could support the use of immunomodulating therapies aimed at restoring T cell function.
Comprehensive Investigation of Immune Cell Responses in Dengue Virus and SARS-CoV-2 Infections: Insight into T, NK and B Cell Dynamics
Gregorova, M. (Author). 23 Jan 2024
Student thesis: Doctoral Thesis › Doctor of Philosophy (PhD)