title: Inflammatory cytokine responses in a pregnant mouse model of Chlamydophila abortus infection.
abstract: Chlamydophila abortus (C. abortus) is the aetiological agent of ovine enzootic abortion (OEA). The highly elevated expression of the pro-inflammatory cytokine tumour necrosis factor-alpha (TNFalpha) and low-level expression of interferon-gamma (IFNgamma) that are detected in C. abortus-infected placentas have been implicated in the pathogenesis of OEA. Late-term abortions similar to those occurring in sheep have also been observed in mouse models of C. abortus infection. Since mouse studies have contributed significantly to our understanding of the immunological responses to chlamydial infections and serve as a good model for rapidly assessing candidate vaccines for OEA, we investigated local expression of TNFalpha and IFNgamma in infected mice. At various time points over the course of infection mice were sacrificed, serum samples obtained for serum antibody and cytokine analyses, and livers and placental tissues were removed and fixed to determine C. abortus colonisation and cytokine expression. Immunostaining for C. abortus was significantly greater in placenta compared to liver (P<0.001), whereas local IFNgamma expression was lower and TNFalpha expression was absent in the placenta compared with the liver across all time points. Serum concentrations of both IFNgamma and TNFalpha increased throughout pregnancy in infected mice. These data suggest that a protective systemic inflammatory immune response controls maternal C. abortus infection but not placental/fetal infection in mice. In contrast to sheep, murine placental TNFalpha expression does not correlate with C. abortus infection, suggesting that the immunopathogenesis of chlamydial abortion differs in these species.
authors.affiliation: Moredun Research Institute, Pentlands Science Park, Bush Loan, Penicuik, Midlothian EH26 0PZ, UK.
authors.forename: Karen
authors.initials: K
authors.lastname: Kerr
authors.forename: Nicholas
authors.initials: N
authors.lastname: Wheelhouse
authors.forename: Morag
authors.initials: M
authors.lastname: Livingstone
authors.forename: Ian E
authors.initials: IE
authors.lastname: Anderson
authors.forename: Gary
authors.initials: G
authors.lastname: Entrican
authors.forename: Declan
authors.initials: D
authors.lastname: McKeever
authors.forename: David
authors.initials: D
authors.lastname: Longbottom
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial; D023501:Chlamydophila / Q000145:classification*; D023521:Chlamydophila Infections / Q000378:metabolism*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000382:microbiology; D051379:Mice; D010920:Placenta / Q000382:microbiology; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014018:Tissue Distribution; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D000942:Antigens, Bacterial; D016207:Cytokines; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma