Inflammatory cytokine responses in a pregnant mouse model of Chlamydophila abortus infection

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 (TNFα) and low-level expression of interferon-gamma (IFNγ) 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 TNFα and IFNγ 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 IFNγ expression was lower and TNFα expression was absent in the placenta compared with the liver across all time points. Serum concentrations of both IFNγ and TNFα 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 TNFα expression does not correlate with C. abortus infection, suggesting that the immunopathogenesis of chlamydial abortion differs in these species.