Chlamydia heat shock protein 60 induces trophoblast apoptosis through TLR4.
Intrauterine infection affects placental development and function, and subsequently may lead to complications such as preterm delivery, intrauterine growth retardation, and preeclampsia; however, the molecular mechanisms are not clearly known. TLRs mediate innate immune responses in placenta, and recently, TLR2-induced trophoblast apoptosis has been suggested to play a role in infection-induced preterm delivery. Chlamydia trachomatis is the etiological agent of the most prevalent sexually transmitted bacterial infection in the United States. In this study, we show that in vitro chlamydial heat shock protein 60 induces apoptosis in primary human trophoblasts, placental fibroblasts, and the JEG3 trophoblast cell line, and that TLR4 mediates this event. We observed a host cell type-dependent apoptotic response. In primary placental fibroblasts, chlamydial heat shock protein 60-induced apoptosis was caspase dependent, whereas in JEG3 trophoblast cell lines it was caspase independent. These data suggest that TLR4 stimulation induces apoptosis in placenta, and this could provide a novel mechanism of pathogenesis for poor fertility and pregnancy outcome in women with persistent chlamydia infection.
Equils
Ozlem
O
Department of Pediatrics, Geffen School of Medicine, University of California-Los Angeles, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA. ozlem.equils@cshs.org
Lu
Daning
D
Gatter
Mary
M
Witkin
Steve S
SS
Bertolotto
Cristina
C
Arditi
Moshe
M
McGregor
James A
JA
Simmons
Charles F
CF
Hobel
Calvin J
CJ
D019138:Antibodies, Blocking / Q000502:physiology; D017209:Apoptosis / Q000276:immunology*; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018834:Chaperonin 60 / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D002690:Chlamydia Infections / Q000276:immunology; D002692:Chlamydia trachomatis / Q000276:immunology*; D004789:Enzyme Activation / Q000276:immunology; D005260:Female; D006801:Humans; D007247:Infertility, Female / Q000276:immunology / Q000382:microbiology; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology / Q000382:microbiology; D051197:Toll-Like Receptor 4 / Q000276:immunology / Q000502:physiology*; D014327:Trophoblasts / Q000201:enzymology / Q000276:immunology* / Q000382:microbiology*
D019138:Antibodies, Blocking; D018834:Chaperonin 60; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; C505407:CASP3 protein, human; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases