Altered innate immunity and damaged epithelial integrity in vaginal microbial dysbiosis

Background: The role of neutrophils relative to vaginal dysbiosis is unclear. We hypothesize that bacterial vaginosis (BV)-associated bacteria may induce the activation and accumulation of mucosal neutrophils within the female reproductive tract (FRT), resulting in epithelial barrier damage.Results: We collected endocervical cytobrushes from women with and without BV andassessed bacteria community type and frequency/functional phenotypes of neutrophils. We performed in vitro whole blood co-cultures with BV-associated bacteria and healthy vaginal commensals and assessed their impact on epithelial integrity using transepithelial electrical resistance. We demonstrated increased neutrophil frequency (p<0.0001), activation (p<0.0001), and prolonged lifespan (p<0.0001) in the cytobrushes from women with non-Lactobacillus dominant (nLD) communities. Our in-vitro co-cultures confirmed these results and identified significant barrier damage in the presence of neutrophils and G. vaginalis.Conclusions: Here, we demonstrate that BV-associated bacteria induce neutrophil activation and increase lifespan, potentially causing accumulation in the FRT and epithelial barrier damage.