Understanding the pathogenicity of Chlamydia pecorum infections in livestock

Md Mominul Islam

doi:10.25907/00014

Chlamydia (C.) pecorum is an obligate intracellular bacterium that is recognized as a ubiquitous and economically significant pathogen of livestock worldwide. In addition to infections in livestock, it infect and causes disease in a wide range of animals, including the iconic Australian marsupial, the koala. While most infections are asymptomatic, C. pecorum can cause clinical disease such as polyarthritis, conjunctivitis and sporadic bovine encephalomyelitis. Molecular typing studies have suggested that C. pecorum strains are genetically diverse and these minor but important genomic differences might be responsible for disease outcomes. Despite all efforts, the pathogenicity of C. pecorum infections in livestock is still not well understood, nor is the in vitro growth kinetics in normal and stress conditions, that reflects the cellular mechanism of C. pecorum infections. Therefore, this PhD aimed to characterise the in vitro developmental cycle of C. pecorum strains in normal and stress conditions, and to develop an in vivo model of C. pecorum infections in sheep. The precise mechanism that Chlamydia use to complete their developmental cycle and exit from the host cell have a direct impact on the ability to infect and disseminate within the host. To understand the growth kinetics, we first evaluated the growth characteristics of five genetically distinct C. pecorum strains and compared their growth in different mammalian epithelial and immune cells. While all the strains exhibited very similar developmental cycle lengths, subtle but important differences were found at the critical timepoints of developmental cycle, including RB/EB conversion, and morphology between the strains. In addition, C. pecorum strains were able to infect and survive in different immune cells. Interferon gamma (IFN-γ) plays an important role in defense against chlamydial infections and in the establishment of persistent infections. Results presented here provides a detailed characterisation of C. pecorum strains in response to IFN-γ and shows that C. pecorum can avoid the inhibitory effects of indoleamine 2,3 dioxygenase (IDO1) dependent IFN-γ induced immune responses in human, and possibly in bovine epithelial cells as well. Results further demonstrated that C. pecorum strains are, unexpectedly sensitive to mouse IFN-γ in mouse fibroblast cells. Finally, an in vivo sheep model was developed and used to understand the infectivity and disease pathogenicity of two different C. pecorum strains, administered via different routes. Results from this study showed that lambs can be infected experimentally, however, there was considerable variation in clinical disease outcome between different C. pecorum strains. Lambs infected with C. pecorum IPA strain, developed more severe arthritis related clinical symptoms, especially lameness, swollen joints and fever. Subsequent necropsy and histopathological examination confirmed the severity of arthritis in IPA infected lambs. Detection of chlamydial DNA in blood and various tissues (liver, spleen, lungs, kidney, brain and lymphonode) in both intra-articular and intravenously infected lambs, suggested systemic dissemination of C. pecorum in lambs. Moreover, lambs infected via IA and IV routes with either strain, developed IgM and IgG antibody responses in the serum after seven and 14 days post inoculation, respectively. This work has contributed valuable information to the existing knowledge of C. pecorum biology and the pathogenicity of C. pecorum infections in animals. Overall, this study demonstrates the critical role of C. pecorum infection dynamics using in vitro and in vivo model.

Understanding the pathogenicity of Chlamydia pecorum infections in livestock

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