Investigation of a mouse and a sheep model to study pathogenic mechanisms of Campylobacter jejuni fetoplacental infection

Abstract

<p>A tetracycline resistant Campylobacter jejuni clone, C. jejuni clone SA (SA for sheep abortion) has replaced C. fetus as the predominant Campylobacter species causing sheep abortion in the United States. The pathogenesis of placental infection caused by this agent and the mechanism of abortion induction are unknown. A primary objective of these studies (chapters 2-5) was to attempt to elucidate important aspects of the pathogenesis of C. jejuni clone SA on the pregnant uterus. Towards this end, several components of this research attempted to characterize aspects of the cellular and molecular pathology of C. jejuni clone SA in the fetoplacental unit and to improve animal models used to study the pathogenesis of this disease. It was found that pregnant laboratory mice can be used as a model to study the reproductive pathology of C. jejuni IA3902, a representative isolate of clone SA, using the endpoint of positive microbial culture of the organism from the fetoplacental unit. Pro-inflammatory and anti-inflammatory cytokines were produced from the C. jejuni infected murine placenta and these could be quantitated in the maternal serum and semi-quantitated in infected reproductive tissues using in situ hybridization. Fetoplacental infection in sheep was established and abortion was induced following intravenous inoculation of C. jejuni IA3902. Sheep placenta infected with C. jejuni IA3902 demonstrated increased caspase 3 expression from stromal cells and trophoblasts and increased expression of Toll-like receptor 4 (TLR4) from trophoblasts of the chorioallantoic membranes.</p>