Ovine trophoblast is a primary source of TNFalpha during Chlamydophila abortus infection.
Chlamydophila abortus is a Gram-negative obligate intracellular bacterium that causes infectious abortion in sheep (ovine enzootic abortion, OEA) and humans. Infected placentas recovered from sheep that experience OEA have thickened membranes, contain dense inflammatory cellular infiltrates and show evidence of intravascular thrombosis. Despite widespread inflammation, chlamydial multiplication is restricted to the chorionic trophoblast cells. To investigate the potential role of trophoblast in the initiation and propagation of placental inflammation during OEA, the AH-1 ovine trophoblast cell line was experimentally infected with C. abortus and analysed for the release of pro-inflammatory mediators. C. abortus was found to induce the release of both tumour necrosis factor-alpha (TNFalpha) and CXCL8 (interleukin-8) from AH-1 cells in a dose- and time-dependent manner. Ultra-violet (UV)-killed organisms did not elicit this profile, indicating that intracellular multiplication of C. abortus was required for release of these pro-inflammatory mediators. Exposure of AH-1 cells to recombinant ovine TNFalpha alone resulted in the release of CXCL8, suggestive of a self-propagating inflammatory cytokine and chemokine cascade. These data indicate a primary role for trophoblast in the initiation and propagation of placental inflammation during chlamydial abortion.
Moredun Research Institute, Pentlands Science Park, Bush Loan, Midlothian, Edinburgh, UK. nick.wheelhouse@moredun.ac.uk
Nick
N
Wheelhouse
Sean
S
Wattegedera
James
J
Stanton
Stephen
S
Maley
Donna
D
Watson
Catherine
C
Jepson
David
D
Deane
David
D
Buxton
David
D
Longbottom
Tim
T
Baszler
Gary
G
Entrican
D000034:Abortion, Veterinary / Q000276:immunology*; D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D023501:Chlamydophila / Q000254:growth & development / Q000276:immunology*; D023521:Chlamydophila Infections / Q000276:immunology / Q000473:pathology / Q000503:physiopathology / Q000662:veterinary*; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006706:Homeostasis / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D016209:Interleukin-8 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology / Q000473:pathology / Q000503:physiopathology / Q000662:veterinary*; D012756:Sheep; D013927:Thrombosis / Q000276:immunology; D014327:Trophoblasts / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha