Cervical mucosal inflammation expands functional polymorphonuclear myeloid-derived suppressor cells

Abstract

Microbial imbalance in the female genital tract increases the risk for adverse health outcomes in women and may increase susceptibility to genital tract infections. The local mucosal immune system plays a fundamental role in maintaining microbial balance. Among different relevant immune subsets, inflammation-induced myeloid-derived suppressor cells (MDSCs) remain understudied in the context of female genital tract conditions. Here we show that frequency of an MDSC subset, Polymorphonuclear (PMN-) MDSCs, increased in the cervical mucosa, but not in blood, of women with Chlamydia trachomatis, bacterial vaginosis, or with a coinfection, but not in women with human papillomavirus. Mucosal PMN-MDSC frequencies correlated with mucosal IL-1β in C. trachomatis patients and ex vivo exposure of cervical tissue to C. trachomatis elevated both PMN-MDSC frequencies and IL-1β secretion. Likewise, exposure of cervical tissue to cervicovaginal lavage fluid from C. trachomatis and bacterial vaginosis patients also enhanced PMN-MDSC frequencies. Lastly, cervical MDSCs expressed suppressive mediators and functionally suppressed cytotoxic T-cell responses. Our study identifies IL-1β-stimulated PMN-MDSCs as an immune suppressive mediator in female genital tract infections, potentially contributing to susceptibility to acquiring secondary infections at this site.