Shortcomings 172 Lack of Full Spectrum of Human Tuberculosis Histopathology 172
INTRODUCTION In the past the rat has been reported to be highly resistant to Mycobacterium tuberculosis (MTB) and thus unattractive as a model of experimental tuberculosis. Early studies showed that high doses of MTB could neither produce tuberculous lesions in the lung nor kill the rats (Gloyne and Page, 1923; Ornstein and Steinbach, 1925). ese observations were followed by a number of studies describing the presence of nonnecrotic tubercles in the lungs of infected rats in association with cutaneous delayed type hypersensitivity (DTH) responses to tuberculin (Long and Vorwald, 1930; Hehre and Freund, 1939). In 1941 Wessels reported that the tuberculosis bacilli could disseminate to dierent organs in the rat and induced DTH in infected animals (Wessels, 1941a,b). In the 1960s rats were reported to be as susceptible to MTB as some strains of mice (Gray, 1961; Flax and Waksman, 1962), and in the 1970s Leord and colleagues showed that MTB-infected rats could generate a specic immune response (Leord et al., 1973). More recently, studies on rats addressed the kinetics of the bacillary load and the histologic response in the lungs (Sugawara et al., 2004a,b, 2006). e following chapter summarizes some of our new microbiological and histological observations in the Wistar rat tuberculosis model.