title: Cutting-edge report: TLR10 plays a role in mediating bacterial peptidoglycan-induced trophoblast apoptosis.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Obstetrics, Gynecology & Reproductive Sciences, Yale University, New Haven, CT, USA.
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Mulla
authors.forename: Kledia
authors.initials: K
authors.lastname: Myrtolli
authors.forename: Serkalem
authors.initials: S
authors.lastname: Tadesse
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Stanwood
authors.forename: Aileen
authors.initials: A
authors.lastname: Gariepy
authors.forename: Seth
authors.initials: S
authors.lastname: Guller
authors.forename: Errol R
authors.initials: ER
authors.lastname: Norwitz
authors.forename: Vikki M
authors.initials: VM
authors.lastname: Abrahams
mesh_terms: D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D001424:Bacterial Infections / Q000150:complications / Q000276:immunology*; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006094:Gram-Positive Bacteria / Q000276:immunology*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D007752:Obstetric Labor, Premature / Q000209:etiology / Q000276:immunology*; D010457:Peptidoglycan / Q000276:immunology; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D051201:Toll-Like Receptor 10 / Q000235:genetics / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000276:immunology; D019076:Transgenes / Q000235:genetics; D014327:Trophoblasts / Q000276:immunology* / Q000382:microbiology
chemical_list: D015850:Interleukin-6; D010457:Peptidoglycan; C475955:TLR10 protein, human; C495342:TLR2 protein, human; D051201:Toll-Like Receptor 10; D051195:Toll-Like Receptor 2; D053148:Caspase 3