Effects of alcohol (EtOH) and Δ9-tetrahydrocannabinol (THC) on early monocyte differentiation: implications for HIV-1 replication

Authors

• SR Abrams
• CE Foster
• C Xie
• JF Reiter
• L Kerosuo

Abstract

Background. Recreational use of marijuana and/or alcohol can modulate host immune networks in response to pathogens. Previously, we found a selective dose-dependent suppression of ex vivo HIV-1 replication in primary macrophages by THC treatment of monocytes during differentiation. In this study, we investigated the molecular consequences of EtOH or THC with EtOH on gene expression profiles during early monocyte differentiation.

Methods. Human peripheral blood monocytes from five healthy donors were exposed ex-vivo to EtOH or THC plus EtOH during differentiation for six hours, one day, or three days. Each treatment and time point mRNA profiles were individually compared to untreated monocytes using microarrays. The limma R package was used for Differential Expression Genes (DEG) analyses. Pathway analyses were completed on DEGs using Qiagen’s Ingenuity Pathways Analysis (IPA).

Results. EtOH pathways were associated with proinflammation. THC pathways were associated with the regulation of immune activation. Through time EtOH and THC treatments shifted monocyte profiles toward metabolic pathways. By day 3, EtOH treatments no longer perturbed proinflammatory pathways in monocytes, while THC treatments continued to regulate or inhibit the monocyte immune activation pathway profile.

Conclusions. EtOH exerts a proinflammatory effect on monocyte gene expression that gradually decreases over time. THC ameliorates the proinflammatory effects of EtOH. Furthermore, THC inhibits immune activation pathways at all time points. Furthermore, THC modifies the immune activation landscape to diminish HIV-1 replication in cells of the monocyte lineage. These ex vivo approaches inform discovery of the complex interactions between substance use, immune function, and HIV-1 replication.

Scientific Focus Area: Virology

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