Microbe-binding antibodies in the female genital tract: associations with the vaginal microbiome and genital immunology

Abstract

Abstract Background Mucosal antibodies in the gut maintain homeostasis between the host and the local microbiome through the clearance of pathogenic bacteria and the development of immune tolerance to inflammatory bacteria. Whether similar bacteria-immunoglobulin interactions modulate cervicovaginal inflammation and/or bacterial colonization in the female genital tract (FGT) is not well understood. Here, we used a flow cytometry-based assay to quantify microbe-binding IgA and IgG in the cervicovaginal secretions of 200 HIV-uninfected women from Nairobi, Kenya that were enriched for bacterial vaginosis (BV) and evaluated the associations of cervicovaginal IgA and IgG with the vaginal microbiome composition and local soluble immune factors. Results Total IgA and IgG were abundant in cervicovaginal secretions and frequently demonstrated ex vivo binding to key vaginal bacteria species Gardnerella vaginalis, Prevotella bivia, Lactobacillus iners, and Lactobacillus crispatus. Microbe-binding antibodies were generally not associated with the presence/absence of the corresponding bacteria. Total and microbe-binding IgA and IgG were inversely correlated with total bacterial abundance and positively correlated with several pro-inflammatory cytokines (IL-6, TNF) and chemotactic chemokines (IP-10, MIG, MIP-1α, MIP-1β, MIP-3α, MCP-1, IL-8), independent of total bacterial abundance. Conclusions Flow cytometry-based quantification of microbe-binding antibodies provides a platform to investigate host-microbiota interactions in the FGT of human observational and interventional studies. In contrast to the gut, cervicovaginal microbe-binding IgA and IgG do not appear to be immunoregulatory but may indirectly mitigate bacteria-induced inflammation by reducing total bacterial abundance.