EXPERIMENTAL INFECTION OF PIGS WITH MYCOBACTERIUM BOVIS AND MYCOBACTERIUM TUBERCULOSIS: TOWARDS A PORCINE MODEL OF HUMAN TUBERCULOSIS
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The study of tuberculosis (TB) pathogenesis has benefitted from the use of animal models like mice, guinea pigs, rabbits, and non-human primates (NHPs). Except for NHP, most animal models have limitations mimicking different aspects of human TB. We propose that the domestic pig, which shares many similarities to humans with respect to pulmonary anatomy, physiology, and immunology, is an equally suitable but more economical alternative to the NHP model. To demonstrate this, groups of mixed-breed domestic pigs were challenged intravenously (IV) with M. tuberculosis or M. bovis and monitored. Pigs were also challenged with high and a low doses of aerosolized M. tuberculosis or M. bovis to mimic the natural route of infection and monitored. We found that pigs challenged intravenously with M. bovis exhibited more severe morbidity and earlier mortality, accompanied by higher tissue bacterial burden and necrosis compared to pigs challenged similarly with M. tuberculosis. Consistently, pigs challenged with high dose aerosolized M. bovis exhibited lower weight gain than pigs challenged similarly with M. tuberculosis. The M. bovis group also exhibited more severe lung pathology and advanced granulomatous lesions compared to the M. tuberculosis group. Pigs challenged specifically with high dose M. bovis exhibited higher bacterial burden and post-primary dissemination. Interestingly, the peripheral IFN-γ responses were similar for both M. bovis and M. tuberculosis challenged pigs, irrespective of the challenge doses. Based on these observations, M. bovis (AF2122/97) is more virulent in domestic pigs than M. tuberculosis (Erdman). Alternatively, domestic pigs seem better at tolerating infection with M. tuberculosis. Nevertheless, either species can be used to model TB in domestic pigs, depending on whether one wishes to recapitulate either an active or a latent TB infection.
DegreeMaster of Science (M.Sc.)
SupervisorChen, Jeffrey M
CommitteeGerdts, Volker; Huang, Yanyun; Rubin, Joseph; Brook, Ryan
Copyright DateApril 2021
Mycobacterium bovis, Mycobacterium tuberculosis, domestic pigs, animal model, tuberculosis