Δ9-Tetrahydrocannabinold (THC) suppresses secretion of IFNα by plasmacytoid dendritic cells (pDC) from healthy and HIV-infected individuals

Plasmacytoid dendritic cells (pDC) play a crucial role in host anti-viral immune response through the secretion of type I interferon. Interferon alpha (IFNα), a type I IFN, is critical for mounting the initial response to viral pathogens. A consequence of Human Immunodeficiency Virus-1 (HIV) infection is a decrease in both pDC number and function, but prolonged pDC activity has been linked with progression from HIV infection to the development of AIDS. HIV patients in the US routinely use cannabinoid-based therapies to combat the side effects of HIV infection and antiretroviral therapy (ART). However, cannabinoids, including Δ 9 -tetrahydrocannabinol (THC), are well-characterized immunosuppressants. Here we report that THC suppressed secretion of IFNα by pDC from both healthy and HIV + donors through a mechanism involving impaired phosphorylation of interferon regulatory factor 7 (IRF-7). These results suggest that THC can suppress pDC function during the early host antiviral by dampening pDC activation.