Lactobacillus crispatus interferes with Chlamydia trachomatis infectivity through modulation of integrin exposure in cervical cells

In women, urogenital CT infections are often asymptomatic, thus remaining unnoticed and untreated. This can lead to complications and sequelae including pelvic inflammatory disease, tubal infertility and ectopic pregnancy (1, 2). A normal vaginal microbiota, dominated by lactobacilli, is crucial for the prevention of several urogenital and sexually transmitted infections, including Chlamydia (3, 4, 5). This aspect is strengthened by the demonstration that in case of bacterial vaginosis, a clinical condition characterized by the depletion of lactobacilli, a higher risk of STI transmission and acquisition is reported (6). This study aimed to elucidate the molecular bases of the interaction among lactobacilli, Chlamydia trachomatis and epithelial cells. We evaluated the capacity of lactobacilli cells and supernatants to interfere with C. trachomatis infectivity in HeLa cells, by means of competition, exclusion and displacement mechanisms. Lactobacilli cells were the most active fraction, by means of an exclusion strategy. We investigated the potential mechanism of protection in Lactobacillus crispatus BC5 (model strain), and we demonstrated that the incubation of HeLa cell line with BC5 cells induces important modifications al the level of the epithelial plasma membrane, by altering lipid composition and α5 integrin subunit exposure. When α5 integrin subunits were masked by a specific blocking antibody, Chlamydia infection was precluded. α5 integrin subunit is thus crucial for the pathogen penetration into HeLa cells, and the anti-Chlamydia activity of BC5 can be directly linked to membrane properties modifications in epithelial cells. In conclusion, we identified a potential molecular mechanism at the basis of the protection exerted by Lactobacillus against the sexually transmitted pathogen Chlamydia trachomatis, getting insights into the role of the vaginal microbiota for the woman’s health