Immune activation and tissue-specific responses related to CMV IgG titers 3141

Abstract Description Cytomegalovirus (CMV) is a chronic infection that alters the immune repertoire, with a large fraction of memory CD4+ and CD8+ T cells dedicated to CMV. While not well-defined or influencing patient care, immune responses to CMV may affect cardiometabolic comorbidities. We examined whether changes in peripheral blood mononuclear cell (PBMCs) subsets associated with CMV seropositivity mirror changes in aortic and perivascular adipose tissue (AT). We collected PBMCs, aorta, and AT samples from individuals undergoing cardiac surgery, used ELISA to stratify CMV IgG as high (>1 IU/ml) or low (<1 IU/ml), and used multiparameter flow cytometry and single-cell RNA-sequencing (scRNA-seq). CMV IgG titers and CX3CR1+, GPR56+, and CD57+/- (CGC+) CD8+ T cells were significantly correlated in PBMCs (p < 0.01) but not aortic tissues (p = 0.2). scRNA-seq of the aorta revealed higher NOS3 in arterial endothelial cells and SPP1 in epiregulin (EREG)-expressing dendritic cells (EREG-DCs) in individuals with high CMV titers. S100A8 was higher in AT EREG-DCs with high CMV titers. There were no differences in PBMCs. The transcriptional differences in EREG-DCs by CMV seropositivity suggest differences in immune inflammation may influence vascular remodeling and homeostasis. This study may provide new insights into CMV-driven mechanisms contributing to vascular pathology and underscore the need for further studies on mechanistic links between CMV infection and, immune dysregulation Topic Categories Immune Response Regulation: Cellular Mechanisms (IRC)