The role of inflammatory factors in the pathogenesis of Mycoplasma bovis pneumonia

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University of Guelph

Bovine respiratory disease (BRD) is a major cause of morbidity and mortality in cattle production worldwide. Mycoplasma bovis is one of the most important pathogens involved in BRD, and it is associated with severe caseonecrotic bronchopneumonia characterized by the presence of necrotic foci with ghost-like cells in the lungs. The pathogenesis of this disease is poorly understood, and the role of inflammation in its development is unclear. This thesis investigates the hypothesis that M. bovis alone does not cause severe disease, but local inflammation at the site of infection exacerbates the development of macrophage cell death and caseonecrotic lesions. The research consisted of two parts: an in vivo experiment using partially colostrum-deprived calves raised in an isolation unit and exposed to various pro-inflammatory factors followed by infection with M. bovis, and an in vitro experiment using bovine monocyte-derived macrophages activated with Mannheimia haemolytica lysate and infected with different M. bovis strains. The in vivo experiment aimed to develop an improved animal model for the study of M. bovis pathogenesis and to evaluate the effects of different inflammatory stimuli on the development and severity of caseonecrotic lesions. The in vitro experiment aimed to determine the type of macrophage cell death initiated by M. bovis, and to compare the cytotoxicity and cytokine production of different M. bovis strains. The results showed that M. bovis infection did not significantly harm macrophages or cause caseonecrotic lesions in the absence of prior inflammation, but it did so when inflammation was induced by live M. haemolytica or bacterial lysates. The results also revealed that M. bovis strains varied in their ability to kill macrophages and induce cytokine expression, and that strains isolated from sick or dead animals tended to be more cytotoxic than those from healthy animals. The results indicate that inflammation is a key factor in the pathogenesis of M. bovis-induced caseonecrotic bronchopneumonia, suggesting that control of harmful inflammatory responses could minimize the severity of this disease. The thesis also suggested directions for future research to elucidate the mechanisms of M. bovis pathogenicity and the immune response to this infection.

Mycoplasma bovis, Caseonecrotic bronchopneumonia, Inflammation, BRD, Neutrophilic bronchiolitis, Bovine monocyte derived macrophages