Cervical mucosal inflammation expands functional polymorphonuclear myeloid-derived suppressor cells

Abstract

The mucosal immune system plays a fundamental role in maintaining microbial balance. Microbial imbalance in the female genital tract increases the risk for adverse health outcomes in women and may increase susceptibility to local infections. Myeloid-derived suppressor cells (MDSCs) remain understudied in the context of female genital tract conditions. Here we show that frequency of polymorphonuclear (PMN-) MDSCs increased in the cervical mucosa of women with Chlamydia trachomatis infection, bacterial vaginosis, or with a coinfection, but not in women with human papillomavirus infection. 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 immunosuppressive mediators in female genital tract infections, potentially modulating susceptibility to local secondary infections.

Keywords: Bacterial vaginosis; Cervical mucosa; Chlamydia trachomatis; Female genital tract infections; Immune suppression; Myeloid-derived suppressor cells.