title: Schistosome egg antigens elicit a proinflammatory response by trophoblast cells of the human placenta.
abstract: Schistosomiasis affects nearly 40 million women of reproductive age. Many of these women are infected while pregnant and lactating. Several studies have demonstrated transplacental trafficking of schistosome antigens; however, little is known regarding how these antigens affect the developing fetus and placenta. To evaluate the impact of schistosomiasis on trophoblasts of the human placenta, we isolated primary trophoblast cells from healthy placentas delivered at term. These trophoblasts were placed in culture and treated with Schistosoma japonicum soluble egg antigens (SEA) or plasma from S. japonicum-infected pregnant women. Outcomes measured included cytokine production and activation of signal transduction pathways. Treatment of primary human trophoblast cells with SEA resulted in upregulation of the proinflammatory cytokines interleukin 6 (IL-6) and IL-8 and the chemokine macrophage inflammatory protein 1α (MIP-1α). Cytokine production in response to SEA was dose dependent and reminiscent of production in response to other proinflammatory stimuli, such as Toll-like receptor 2 (TLR2) and TLR4 agonists. In addition, the signaling pathways extracellular signal-regulated kinase 1/2 (ERK1/2), Jun N-terminal protein kinase (JNK), p38, and NF-κB were all activated by SEA in primary trophoblasts. These effects appeared to be mediated through both carbohydrate and protein epitopes of SEA. Finally, primary trophoblasts cocultured with plasma from S. japonicum-infected pregnant women produced increased levels of IL-8 compared to trophoblasts cocultured with plasma from uninfected pregnant women. We report here a direct impact of SEA on primary human trophoblast cells, which are critical for many aspects of a healthy pregnancy. Our data indicate that schistosome antigens can activate proinflammatory responses in trophoblasts, which might compromise maternal-fetal health in pregnancies complicated by schistosomiasis.
authors.affiliation: Center for International Health Research, Rhode Island Hospital, Brown University Medical School, Providence, Rhode Island, USA. emcdonald1@lifespan.org
authors.forename: Emily A
authors.initials: EA
authors.lastname: McDonald
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Kurtis
authors.forename: Luz
authors.initials: L
authors.lastname: Acosta
authors.forename: Fusun
authors.initials: F
authors.lastname: Gundogan
authors.forename: Surendra
authors.initials: S
authors.lastname: Sharma
authors.forename: Sunthorn
authors.initials: S
authors.lastname: Pond-Tor
authors.forename: Hai-Wei
authors.initials: HW
authors.lastname: Wu
authors.forename: Jennifer F
authors.initials: JF
authors.lastname: Friedman
mesh_terms: D000328:Adult; D000818:Animals; D000947:Antigens, Helminth; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D010920:Placenta / Q000166:cytology*; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic; D012549:Schistosoma japonicum / Q000276:immunology*; D012552:Schistosomiasis / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D014327:Trophoblasts / Q000469:parasitology*
chemical_list: D000947:Antigens, Helminth; D016207:Cytokines