Immunopathology of Chlamydophila abortus infection in a pregnant mouse model

Abstract

Chlamydophila abortus targets the ovine placenta, causing tissue damage, inflammation and abortion. C. abortus is the main infectious cause of abortion in ewes in the UK and results in major economic losses to the sheep industry. A pregnant mouse model was developed to investigate immune responses and disease pathogenesis for comparison with the ovine disease.Pregnant mice were inoculated at mid-gestation with C. abortus to investigate progression and pathogenesis of infection. This resulted in abortion on days 6-8 post¬ infection (p.i.). Infected cells were identified at the maternal-foetal interface on days 3 and 5 p.i. and chlamydial inclusions were scattered throughout the trophoblastic labyrinth of the placenta between days 3 and 7 p.i.. Infected areas were accompanied by a maternal mononuclear inflammatory cellular infiltrate, including polymorphonuclear neutrophils, B cells and CD4 and CD8 T cells. C. abortus organisms were cultured from both maternal and foetal tissues, higher numbers present in placenta, the target organ.A Thl type immune response was characterised in the mouse model, similar to that in ovine infections. A dominant IgG2a antibody response was identified and IFN-y and TNF-a expression were detected in both sera and supernatants from stimulated splenocytes. IFN-y mRNA and TNF-a mRNA expression were detected by in situ hybridisation in mouse tissues infected with C. abortus. A latent/subclinical persistent infection did not appear to develop in non-pregnant mice infected with C. abortus and abortion did not occur in the subsequent pregnancy, in contrast to that in ovine infections. Repeat abortion did not occur in the pregnancy subsequent to abortion in mice, similar to the situation observed in sheep. Mice were also immune to secondary infection in the pregnancy subsequent to abortion.Infection of pregnant mice resulted in abortion as observed in infected ewes, and a similar Thl immune response is elicited in both sheep and mice. This model will allow the rapid screening of novel protein and DNA based vaccines to protect against chlamydial abortion

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