YAP1 induces marrow derived suppressor cell recruitment in Chlamydia trachomatis infection

Abstract

Chlamydia trachomatis (C. trachomatis) is the most commonly diagnosed bacterial sexually transmitted infection (STI) worldwide. Marrow derived suppressor cells (MDSCs) are a heterogeneous population of immature monocytes and granulocytes, which are effective inhibitors for T cell activation. This study explores the role of MDSCs in the immune escape mechanism of C. trachomatis. We established a vaginal infection model of a BALB/c-Chlamydia trachomatis mouse pneumonia strain (MoPn), and compared the percentages of MDSCs, CD4+T, and CD8+T cells in the spleen and cervix of mice before and after infection. The expression levels of arginase-1 (Arg-1) and inducible nitric oxide synthase (iNOS) in MDSCs, and the expression level of transcriptional co-activator yes-associated protein 1 (YAP1) in the cervix were also compared. The results show that the proportion of MDSCs increases, while the proportion of CD4+T and CD8+T cells decreases after C. trachomatis-infection. The expression of Arg-1 and iNOS in MDSCs and YAP1 in host cells is up-regulated. C. trachomatis growth is inhibited after the inhibition of YAP1 in host cells. The proportion of MDSCs decreases after in vivo pharmacological inhibition of YAP1 in the C. trachomatis-infected mouse model. These results demonstrate, for the first time, the participation of MDSC in the immune escape of C. trachomatis under the action of YAP1.