Experimental infection of pigs with Mycobacterium bovis and M. tuberculosis: Towards a model of human tuberculosis
Nirajan Niroula*1, 2 & Jeffrey Chen1, 2
1. Vaccine and Infectious Disease Organization-International Vaccine Centre (VIDO-InterVac), University of Saskatchewan, Saskatoon Canada
2. Department of Veterinary Microbiology, University of Saskatchewan, Saskatoon Canada
Our current understanding of TB pathogenesis relies heavily on studies in animal models such as mice, guinea pigs, rabbits and non-human primates (NHPs). However, with the exception of non-human primates (NHP), most animal models have limitations in mimicking different aspects of human TB. We hypothesized that the domestic pig, which shares many similarities to humans with respect to its pulmonary anatomy, physiology and immunology, can be an equally suitable but more economical alternative to the NHP model. To test this, groups of mixed breed domestic pigs were first challenged intravenously (IV) with M. tuberculosis or M. bovis and monitored. Subsequently, groups of pigs were challenged with high and a low doses of aerosolized M. tuberculosis or M. bovis to mimic the natural route of infection and monitored.
We observed that pigs challenged with M. bovis by the IV route exhibited earlier mortality and more severe morbidity, higher tissue bacterial burden and tissue necrosis compared to pigs challenged similarly with M. tuberculosis. Consistently, pigs challenged with high dose M. bovis by the aerosol route exhibited significantly 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 compared to M. tuberculosis infected pigs. 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 appears to be more virulent in domestic pigs than 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.