What animal models can teach us about the pathogenesis of tuberculosis in humans

Abstract: Technology is currently available which permits the reproducible infection of laboratory animals with virulent tubercle bacilli under conditions simulating those under which man is infected. This technology has been used to investigate a series of fundamental questions about the pathogenesis of tuberculosis. An integrated view of the pathogenesis of tuberculosis has been constructed which combines studies from animal models and our understanding of the key events in the development of cavitary pulmonary tuberculosis in man. This view, developed as a guide to further hypothesis testing, indicates that whether cavitary pulmonary tuberculosis develops by endogenous reactivation or by exogenous reinfection is determined solely by the route by which the tubercle bacillus reaches the apical-subapical region of the lung. It is in this region that the bacillus survives the cell mediated immune response. This view of the pathogenesis of tuber-culosis permits identification of the factors in a given geographic region governing the probability that cavitary pulmonary tuberculosis develops by one or the other pathway. Knowledge of these factors permits the identification of the appropriate tuberculosis control strategies. After a brief commentary on past contri-butions of animal models to our understandin