Microbe-binding Antibodies in the Female Genital Tract: Associations with the Vaginal Microbiome and Genital Immunology

Abstract

Bacteria-Ig interactions maintain homeostasis in the gut through the clearance of pathogenic bacteria and the development of immune tolerance to inflammatory bacteria; whether similar interactions modulate inflammation and bacterial colonization in the female genital tract is uncertain. In this study, 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. Total IgA and IgG were abundant and frequently demonstrated ex vivo binding to the key vaginal bacteria species Gardnerella vaginalis, Prevotella bivia, Lactobacillus iners, and Lactobacillus crispatus, which are largely microbe-specific. Microbe-binding Abs were generally not associated with the presence or abundance of their corresponding bacteria. Total and microbe-binding IgA and IgG were inversely correlated with total bacterial abundance and positively correlated with several proinflammatory 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. Flow cytometry-based quantification of microbe-binding Abs provides a platform to investigate host-microbiota interactions in the female genital tract 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.