Cutting-edge report: TLR10 plays a role in mediating bacterial peptidoglycan-induced trophoblast apoptosis

Am J Reprod Immunol. 2013 May;69(5):449-53. doi: 10.1111/aji.12065. Epub 2012 Dec 28.

Abstract

Problem: There is a strong correlation between intrauterine bacterial infection and preterm labor. While inflammation is a common mechanism, certain pathogens may trigger placental apoptosis. TLR2 activation by gram-positive bacterial peptidoglycan (PDG) induces first-trimester trophoblast apoptosis and decreased IL-6 secretion. This is dependent upon the presence of TLR1 and the absence of TLR6 and both TLR2 coreceptors. As TLR10 is also a TLR2 coreceptor, the objective of this study was to determine its expression and function in the trophoblast.

Method of study: First-and third-trimester human placental tissue and isolated trophoblast were evaluated for TLR10 expression. A first-trimester human trophoblast cell line stably transfected with a TLR10 dominant negative (TLR10-DN) or vector control was treated with or without PDG and analyzed for apoptosis and IL-6.

Results: TLR10 was expressed by trophoblasts during the first and third trimesters of pregnancy. PDG-induced trophoblast caspase-3 activity was inhibited by the presence of the TLR10-DN. The presence of the TLR10-DN had no effect on PDG reduction in trophoblast IL-6 secretion.

Conclusion: This study demonstrates that trophoblast TLR10 plays a role in promoting apoptosis triggered by gram-positive bacterial components and suggests that TLR10 may regulate the balance between trophoblast survival and cell death.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Apoptosis / genetics
  • Apoptosis / immunology
  • Bacterial Infections / complications
  • Bacterial Infections / immunology*
  • Caspase 3 / metabolism
  • Cell Line
  • Female
  • Gene Expression Regulation, Developmental
  • Gram-Positive Bacteria / immunology*
  • Humans
  • Interleukin-6 / metabolism
  • Mutation / genetics
  • Obstetric Labor, Premature / etiology
  • Obstetric Labor, Premature / immunology*
  • Peptidoglycan / immunology
  • Pregnancy
  • Pregnancy Trimester, First
  • Toll-Like Receptor 10 / genetics
  • Toll-Like Receptor 10 / metabolism*
  • Toll-Like Receptor 2 / immunology
  • Transgenes / genetics
  • Trophoblasts / immunology*
  • Trophoblasts / microbiology

Substances

  • Interleukin-6
  • Peptidoglycan
  • TLR10 protein, human
  • TLR2 protein, human
  • Toll-Like Receptor 10
  • Toll-Like Receptor 2
  • Caspase 3