Toll-like receptor-mediated responses by placental Hofbauer cells (HBCs): a potential pro-inflammatory role for fetal M2 macrophages

Am J Reprod Immunol. 2015 Jan;73(1):22-35. doi: 10.1111/aji.12336. Epub 2014 Oct 24.

Abstract

Problem: 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.

Method of study: 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.

Conclusion: 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.

Keywords: Hofbauer cells; TLRs; macrophages; placenta.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Chorionic Villi / immunology*
  • Female
  • Fibroblasts / immunology
  • Human Umbilical Vein Endothelial Cells / immunology
  • Humans
  • Inflammation Mediators / metabolism
  • Interleukin-6 / metabolism
  • Interleukin-8 / metabolism
  • Lipopolysaccharide Receptors / metabolism
  • Lipopolysaccharides / immunology
  • Lymphocyte Antigen 96 / metabolism
  • Macrophages / immunology*
  • Poly I-C / immunology
  • Pregnancy
  • Toll-Like Receptors / genetics
  • Toll-Like Receptors / metabolism*
  • Up-Regulation

Substances

  • Inflammation Mediators
  • Interleukin-6
  • Interleukin-8
  • Lipopolysaccharide Receptors
  • Lipopolysaccharides
  • Lymphocyte Antigen 96
  • Toll-Like Receptors
  • Poly I-C