HIV infection and use of illicit substances promote secretion of semen exosomes that reprogram monocyte morphology

ABSTRACT: HIV transmission involves the adhesion to and migration of infected cells, including monocytes across biological barriers comprising extracellular matrix components. Recently, semen exosomes (SE) from HIV uninfected (HIV-) and HIV infected (HIV+) subjects were shown to contain molecules that were adhesive to Jurkat T cells. Since monocyte trafficking across various biological barriers are intensified by HIV and/or illicit substances, such as cocaine, we sought to understand how SE from HIV infected subjects’ comorbid with illicit drug abuse influence monocyte gene expression and behavior. Therefore, a model of U937 monocyte adhesion on collagen-coated surface in the presence and absence of SE from various clinical (HIV-Drug-, HIV-Drug+, HIV+Drug-, and HIV+Drug+) groups was developed. Using this system, we demonstrate by Microarray analysis that SE from different clinical groups reprogramed gene expression profile of monocytes cultured atop collagen. In line with altered gene expression is increased adhesion of monocytes to collagen following treatment with SE from all clinical groups compared to vehicle. Interestingly, SE from HIV+ subjects’ comorbid with drug abuse potentiated monocyte adhesion to collagen. Mechanistically, SE-Drug and SE-HIV altered monocyte shape, induced actin cytoskeleton reorganization, formation of membrane ruffles and lamellipodia-like structures, as well as focal-adhesion contacts. The cytoskeletal reorganization induced by SE-Drug is associated with impairment of cell motility, while SE-HIV increased cell chemotaxis toward HIV secretome. The observation of SE-Drug and SE-HIV mediated alteration of monocyte transcriptome and cellular behavior reported herein is key to understanding the contribution of exosomes to long-term neuro, vascular, and mucosal perturbations associated with psychostimulants (methamphetamine, cocaine, opioids, and alcohol) comorbidity with HIV infection.

ORGANISM(S): Homo sapiens

PROVIDER: GSE129506 | GEO | 2019/09/20

REPOSITORIES: GEO