BCG vaccination in the cotton rat (Sigmodon hispidus) infected by the pulmonary route with virulent Mycobacterium tuberculosis

To evaluate the usefulness of the American cotton rat (Sigmodon hispidus) in the evaluation of vaccine-induced resistance, we infected BCG-vaccinated and non-vaccinated cotton rats with Mycobacterium tuberculosis (H37Rv) via the respiratory route. Lung histopathology of these animals showed loose, disorganized granulomas which were non-necrotic up to 8 weeks post-infection. Moreover, we were not able to detect a DTH response after intradermal injection with PPD antigen. Prior BCG vaccination significantly reduced lung and spleen bacterial loads by 1-1.5 log CFU and upregulated PPD-induced proliferation and production of IFNγ in lymphocyte cultures. We conclude that pulmonary infection of the cotton rat with Mtb more closely resembles the phenotype seen in mice rather than guinea pigs.