title: Toll-like receptor-mediated responses by placental Hofbauer cells (HBCs): a potential pro-inflammatory role for fetal M2 macrophages.
abstract: OBJECTIVE
  Microbial-driven responses in placenta are linked with adverse pregnancy outcomes. The role of Toll-like receptor (TLR) function in Hofbauer cells (HBCs) and fetal macrophages of the placental villous core remains understudied.
  
  
  METHODS
  Flow cytometry and immunohistochemistry (IHC) were used to establish the phenotype of HBCs. Regulation of cytokine secretion in response to treatment with TLR agonists and expression levels of TLRs and co-activators were compared in HBCs, placental fibroblasts (FIBs), and human umbilical vein endothelial cells (HUVECs) using ELISA and qPCR.
  
  
  RESULTS
  Although flow cytometry and IHC revealed HBCs to be M2 (anti-inflammatory) macrophages, LPS and polyinosinic: polycytidylic acid [poly (I:C)] treatments markedly enhanced IL-6 secretion by HBCs, and expression of TLR-2, TLR-3, TLR-4, CD14, and MD-2 was the highest in HBCs.
  
  
  CONCLUSIONS
  These results indicate that although HBCs are M2 macrophages, inflammatory responses are induced through TLR-3 and TLR-4 in this cell type, suggesting a role in microbial-driven placental/fetal inflammation.
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Omar M
authors.initials: OM
authors.lastname: Young
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Tang
authors.forename: Tracy
authors.initials: T
authors.lastname: Niven-Fairchild
authors.forename: Serkalem
authors.initials: S
authors.lastname: Tadesse
authors.forename: Graciela
authors.initials: G
authors.lastname: Krikun
authors.forename: Errol R
authors.initials: ER
authors.lastname: Norwitz
authors.forename: Gil
authors.initials: G
authors.lastname: Mor
authors.forename: Vikki M
authors.initials: VM
authors.lastname: Abrahams
authors.forename: Seth
authors.initials: S
authors.lastname: Guller
mesh_terms: D002478:Cells, Cultured; D002824:Chorionic Villi / Q000276:immunology*; D005260:Female; D005347:Fibroblasts / Q000276:immunology; D061307:Human Umbilical Vein Endothelial Cells / Q000276:immunology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D051218:Lymphocyte Antigen 96 / Q000378:metabolism; D008264:Macrophages / Q000276:immunology*; D011070:Poly I-C / Q000276:immunology; D011247:Pregnancy; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D018836:Inflammation Mediators; D015850:Interleukin-6; D016209:Interleukin-8; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D051218:Lymphocyte Antigen 96; D051193:Toll-Like Receptors; D011070:Poly I-C
keywords: Hofbauer cells; TLRs; macrophages; placenta