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

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 may affect a woman's reproductive health, including her risk of acquiring HIV.

Dysbiosis-induced IL-33 contributes to impaired antiviral immunity in the genital mucosa

“…In contrast, our results suggest that dysbiosis rather than reduction of commensal microbiota are more likely to contribute to impairment of protective immunity against mucosal HSV-2 infection. Recent human study also supports that high diversity vaginal microbiome correlates with high susceptibility to genital infections (14). Inoculation of Toll-like receptor agonists to reconstitute the effects of commensal bacteria could not restore immune responses in our study, but this treatment completely restored antiviral immunity in other studies (3,4).…”

“…In vaginal ecosystems, a low diversity of bacterial communities (dominated by Lactobacillus species) seems to represent a healthy vaginal flora (13,14). In contrast, low diversity of the gut microbiota has been considered as a causative factor for inflammatory bowel disease (15).…”

The Human Microbiome during Bacterial Vaginosis

“…G. vaginalis was also one of the six dominant species identified by 16S rRNA gene sequencing in a microbiota community type distinguished by higher cervicovaginal levels of IL-1␣, IL-␤, IL-8, TNF-␣, IFN-␥, and IL-10 in young South Africans at risk of HIV (75). A recent 16S rRNA gene analysis confirmed that a high abundance of Gardnerella in particular, combined with a low abundance of Lactobacillus, may contribute to the increased risk of preterm birth (76).…”

“…Although inconsistent effects on cytokines, e.g., IL-6 and TNF-␣, have been reported (69,85) (70). In clinical studies, the detection of A. vaginae in vaginal swabs was correlated with higher levels of the same inflammatory mediators that were associated with G. vaginalis (74), and Atopobium was among the taxa most abundant in microbiota community types distinguished by the highest levels of cervicovaginal inflammatory mediators in a study of South African women (75).…”

Treatment of vaginal atrophy with estriol and lactobacilli combination: a clinical review

“…Probiotics also show immune-modulating properties 7,63 -vaginal lactobacilli properly calibrate genital immune system responses via specific signaling processes 67,68 . Postmenopausal women with diminished estrogen levels have quite different vaginal flora compared to premenopausal women.…”