Evaluating the in vivo effects of Aspirin on vaginal inflammation and barrier function

Inflammation is an important component of protective immunity in the lower female genital tract but must be tightly regulated to limit host tissue damage. In this study, we evaluated the in vivo potential of the anti-inflammatory drug Acetylsalicylic Acid (ASA) to lower proinflammatory cytokine production, restore vaginal barrier integrity and reduce the frequency of activated T cells that serve as targets for HIV infection. Daily intraperitoneal administration of ASA in mice had no effect on epithelial layer structure and CD4⁺ T cell activation status at homeostasis but significantly reduced barrier disruption in response to inflammatory bacteria Mobiluncus mulieris (M. muleiris). ASA treatment lowered the frequency of activated CXCR6⁺ T_H17 subsets in the vaginal mucosa in response to M. muleiris and Gardnerella vaginalis challenge, also reducing the number of CCR5⁺ T cells in the latter. RNAseq analysis of the draining lymph nodes indicate that ASA treatment modulates immunologic and metabolic pathways associated with inflammation, cytokine signaling and cell-cell junction proteins. Our data indicate that ASA administration may reduce inflammation and help restore vaginal homeostasis in mice and aligns with human cohort studies evaluating the potential for oral ASA to reduce HIV transmission.