Enhanced TLR7-induced interferon responses in women living with HIV

IntroductionBiological sex is a key modifier of HIV pathogenesis, with women more frequently achieving spontaneous viral control than men. Toll-like receptor 7 (TLR7), an endosomal RNA sensor encoded on the X chromosome that escapes X-inactivation, plays a pivotal role in antiviral immunity and is increasingly targeted in HIV cure strategies aimed at reversing viral latency.

However, it remains unclear whether TLR7-driven immune responses differ by sex in the context of HIV infection.MethodsWe characterized sex-specific immune responses to TLR7 stimulation in a cohort of 1,326 antiretroviral therapy (ART)-suppressed individuals living with HIV (192 women, 1,134 men), including 50 spontaneous HIV controllers, and in 43 people living without HIV (28 women, 15 men). Peripheral blood mononuclear cells (PBMCs) were stimulated ex vivo with the TLR7 agonist imiquimod (IMQ), followed by cytokine profiling and transcriptome analysis by RNA sequencing.