Bacterial chorioamnionitis causes adverse pregnancy outcomes yet host-microbial interactions are not well characterized within gestational membranes. The decidua, the outermost region of the membranes, is a potential point of entry for bacteria ascending from the vagina to cause chorioamnionitis. We sought to determine whether paracrine communication between decidual stromal cells and macrophages shaped immune responses to microbial sensing.
Decidual cell-macrophage interactions were modeled in vitro utilizing decidualized, telomerase-immortalized human endometrial stromal cells (dTHESCs) and phorbol ester-differentiated THP-1 macrophage-like cells. The production of inflammatory mediators in response to LPS was monitored by ELISA for both cell types, while phagocytosis of bacterial pathogens ( E. coli and Group B Streptococcus (GBS)) was measured in THP-1 cells or primary human placental macrophages. Diclofenac, a nonselective cyclooxygenase inhibitor, and prostaglandin E 2 (PGE 2) were utilized to interrogate prostaglandins as decidual cell-derived paracrine immunomodulators. A mouse model of ascending chorioamnionitis caused by GBS was utilized to assess the co-localization of bacteria and macrophages in vivo and assess PGE 2 production.
In response to LPS, dTHESC and THP-1 co-culture demonstrated enhancement of most inflammatory mediators, but a potent suppression of macrophage TNF-α generation was observed. This appeared to reflect a paracrine-mediated effect of decidual cell-derived PGE 2. In mice with GBS chorioamnionitis, macrophages accumulated at sites of bacterial invasion with increased PGE 2 in amniotic fluid, suggesting such paracrine effects might hold relevance in vivo.