Experimental tuberculosis: the role of comparative pathology in the discovery of improved tuberculosis treatment strategies

Abstract

The use of laboratory animals is critical to the discovery and in vivo pre-clinical testing of new drugs and drug combinations for use in humans. M. tuberculosis infection of mice, rats, guinea pigs, rabbits and non-human primates are the most commonly used animal models of human tuberculosis. While granulomatous inflammation characterizes the most fundamental host response to M. tuberculosis aerosol infection in humans and animals, there are important species differences in pulmonary and extra-pulmonary lesion morphology which may influence responses to drug therapy. Lesions that progress to necrosis or cavitation are common, unfavorable host responses in naturally occurring tuberculosis of humans, but are not seen consistently in experimental infections in most animal model species. The importance of these unique lesion morphologies is that they represent irreversible tissue damage that can harbor persistent bacilli which are difficult to treat with standard therapies. Understanding the differences in host response to experimental tuberculosis infections may aid in selecting the most appropriate animal models to test drugs that have been rationally designed to have specific mechanisms of action in vivo. A better understanding of lesion pathogenesis across species may also aid in the identification of novel therapeutic targets or strategies that can be used alone or in combination with more conventional tuberculosis treatments in humans.