Distinct effects of the cervico-vaginal microbiota and herpes simplex type 2 infection on female genital tract immunology

Genital inflammation is a key determinant of HIV transmission risk, and may alter both epithelial integrity and the presence of HIV-susceptible target cells. Bacterial sexually transmitted infections (STIs) and herpes simplex type 2 (HSV-2) alter genital immunology and increase HIV risk, so we assessed the interaction between the genital microbiota, HSV-2 and immune cell and cytokine alterations known to enhance HIV susceptibility. Cervico-vaginal secretions were collected by Instead Softcup and endocervical cells by cytobrush. T cell and dendritic cell subsets were assessed by flow cytometry, cytokine levels by multiplex ELISA, and the composition of the microbiota by 16S rRNA genes sequencing. The structure of the cervico-vaginal microbiota of 51 participants was composed of community state types (CSTs) showing diversity (20/51; 39%) or predominated by Lactobacillus iners (22/51; 42%), L. crispatus (7/51; 14%) or L. gasseri (2/51; 4%). High diversity CSTs were strongly associated with increased cervico-vaginal pro-inflammatory cytokines, but not with altered endocervical T cell subsets or dendritic cell populations. However, cervical CD4+ T cell number was associated with HSV-2 infection status and a distinct cytokine profile. This suggests that the genital microbiota and HSV-2 infection may influence HIV susceptibility through distinct biological mechanisms.