title: A role for TLRs in the regulation of immune cell migration by first trimester trophoblast cells.
abstract: Normal pregnancy is characterized by the presence of innate immune cells at the maternal-fetal interface. Originally, it was postulated that the presence of these leukocytes was due to an immune response toward paternal Ags expressed by the invading trophoblasts. Instead, we and others postulate that these innate immune cells are necessary for successful implantation and pregnancy. However, elevated leukocyte infiltration may be an underlying cause of pregnancy complications, such as preterm labor or preeclampsia. Furthermore, such conditions have been attributed to an intrauterine infection. Therefore, we hypothesize that first trimester trophoblast cells, upon recognition of microbes through TLRs, may coordinate an immune response by recruiting cells of the innate immune system to the maternal-fetal interface. In this study, we have demonstrated that human first trimester trophoblast cells constitutively secrete the chemokines growth-related oncogene, growth-related oncogene alpha, IL-8, and MCP-1 and are able to recruit monocytes and NK cells, and to a lesser degree, neutrophils. Following the ligation of TLR-3 by the viral ligand, poly(I:C), or TLR-4 by bacterial LPS, trophoblast secretion of chemokines is significantly increased and this in turn results in elevated monocyte and neutrophil chemotaxis. In addition, TLR-3 stimulation also induces trophoblast cells to secrete RANTES. These results suggest a novel mechanism by which first trimester trophoblast cells may differentially modulate the maternal immune system during normal pregnancy and in the presence of an intrauterine infection. Such altered trophoblast cell responses might contribute to the pathogenesis of certain pregnancy complications.
authors.affiliation: Department of Obstetrics, Gynecology & Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Vikki M
authors.initials: VM
authors.lastname: Abrahams
authors.forename: Irene
authors.initials: I
authors.lastname: Visintin
authors.forename: Paulomi B
authors.initials: PB
authors.lastname: Aldo
authors.forename: Seth
authors.initials: S
authors.lastname: Guller
authors.forename: Roberto
authors.initials: R
authors.lastname: Romero
authors.forename: Gil
authors.initials: G
authors.lastname: Mor
mesh_terms: D018925:Chemokines / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D007962:Leukocytes / Q000276:immunology; D011247:Pregnancy / Q000276:immunology*; D011261:Pregnancy Trimester, First; D051196:Toll-Like Receptor 3 / Q000378:metabolism; D051193:Toll-Like Receptors / Q000502:physiology*; D014327:Trophoblasts / Q000378:metabolism*
chemical_list: D018925:Chemokines; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D051193:Toll-Like Receptors