Abstract

As many mononuclear cells from Mycobacterium tuberculosis-infected lung tissues are not available for fluorescence-activated cell sorter (FACS) analysis and the tuberculin test is not feasible in a mouse tuberculosis model, we attempted to develop a rat tuberculosis model. We have previously reported that rat tuberculosis is associated with granulomas that lack central necrosis. In order to develop a better animal model of tuberculosis in immunocompromised humans (tuberculosis associated with HIV infection or tuberculosis of the elderly), we infected F344/N-rnu nude rats with M. tuberculosis via the airborne route. The animals developed pulmonary granulomas with central necrosis encapsulated by dense collagen fibres, closely resembling those of human tuberculosis. The nude rats died of disseminated tuberculosis by the 85th day after aerosol infection, while F344 wild-type rats did not. Interestingly, T-cells that were reactive with anti-CD4 antibody and anti-CD8 antibody, indicating the presence of remnant thymus, were observed in the infected lung tissues of the nude rats. Therefore, T-cell precursors may be present in nude rats. The nude rat tuberculosis model mimics tuberculosis in immunocompromised humans and may provide a suitable model for immunological studies in vivo.

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