Activated NK Cells with Pro-inflammatory Features are Associated with Atherogenesis in Perinatally HIV-Acquired Adolescents

Abstract

Human immunodeficiency virus (HIV) is associated with persistent immune activation and dysfunction in people with HIV despite treatment with antiretroviral therapy (ART). Modulation of the immune system may be driven by: low-level HIV replication, co-pathogens, gut dysbiosis /translocation, altered lipid profiles, and ART toxicities. In addition, perinatally acquired HIV (PHIV) and lifelong ART may alter the development and function of the immune system. Our preliminary data and published literature suggest reprogramming innate immune cells may accelerate aging and increase the risk for future end-organ complications, including cardiovascular disease (CVD). The exact mechanisms, however, are currently unknown. Natural killer (NK) cells are a highly heterogeneous cell population with divergent functions. They play a critical role in HIV transmission and disease progression in adults. Recent studies suggest the important role of NK cells in CVDs; however, little is known about NK cells and their role in HIV-associated cardiovascular risk in PHIV adolescents. Here, we investigated NK cell subsets and their potential role in atherogenesis in PHIV adolescents compared to HIV-negative adolescents in Uganda. Our data suggest, for the first time, that activated NK subsets in PHIV adolescents may contribute to atherogenesis by promoting plasma oxidized low-density lipoprotein (Ox-LDL) uptake by vascular macrophages.

Exercise to Prevent Accelerated Vascular Aging in People Living With HIV

“…187 Recent evidence also suggests that several subsets of natural killer cells are activated in PLWH on ART, which promotes oxidized low-density lipoprotein uptake by tissue macrophages, potentially contributing to accelerated atherosclerotic development. 188 Finally, reduced thymic output-a hallmark of thymic involution due to aging-has been identified as a mechanism that also contributes to incomplete immune reconstitution following initiation of ART. 154 Overall, these findings suggest that excess CVD morbidity and mortality among PLWH on ART is at least partially attributable to chronic immune activation and premature immunosenescence, contributing to accelerated vascular aging.…”