Cervicovaginal Bacteria Are a Major Modulator of Host Inflammatory Responses in the Female Genital Tract

TLDR

Lactobacillus colonization is essential for genital health, yet the impact of genital microbiota on immune function and disease susceptibility remains poorly understood. The study aims to elucidate how cervicovaginal microbiota influence genital inflammation and reproductive health, including HIV acquisition risk. Transcriptional profiling indicates that gram‑negative bacterial products activate Toll‑like receptor 4 on antigen‑presenting cells, triggering NF‑κB signaling and chemokine‑mediated lymphocyte recruitment to drive inflammation. Women with high‑diversity, low‑Lactobacillus communities exhibited markedly elevated pro‑inflammatory cytokines, a relationship confirmed longitudinally and linking microbial diversity to inflammatory activation.

Abstract

Colonization by Lactobacillus in the female genital tract is thought to be critical for maintaining genital health. However, little is known about how genital microbiota influence host immune function and modulate disease susceptibility. We studied a cohort of asymptomatic young South African women and found that the majority of participants had genital communities with low Lactobacillus abundance and high ecological diversity. High-diversity communities strongly correlated with genital pro-inflammatory cytokine concentrations in both cross-sectional and longitudinal analyses. Transcriptional profiling suggested that genital antigen-presenting cells sense gram-negative bacterial products in situ via Toll-like receptor 4 signaling, contributing to genital inflammation through activation of the NF-κB signaling pathway and recruitment of lymphocytes by chemokine production. Our study proposes a mechanism by which cervicovaginal microbiota impact genital inflammation and thereby might affect a woman's reproductive health, including her risk of acquiring HIV.