The Mendelian segregation of resistance to infection in different strains of mice infected with mycobacteria, Salmonella and Leishmania spp, all ofwhich live in macrophages, is currently under close scrutiny. Here, Erwin Schurr and colleagues review the nature and function of the Beg gene in controlling innate resistance to mycobacterial infection in mice and speculate on the occurrence of a possible human equivalent.
According to estimates by the World Health Organization, about 100 million people are infected with Mycobacterium tuberculosis, 10 million of which develop clinical forms of tuberculosis resulting in three million deaths annually'-3. Ten to 15 million people suffer from leprosy, a chronic debilitating mycobacterial (M. leprae) disease that can result in extensive physical deformation'. Effective chemotherapeutic treatment is available for both diseases; however, it is not routinely available in less developed areas, is dependent on long-term compliance to the drug regimen and is complicated by the emergence of drug-resistant mycobacteria. Consequently, the control of tuberculosis and leprosy relies heavily on vaccination program$. By far the most common vaccine for this purpose is an attenuated strain of Mycobacterium bovis Bacille Calmette Guerin (BCG), which has been used for almost 70 year@. One of the unsolved problems in vaccine immunology is the variable efficacy of BCG vaccination against tuberculosis and leprosy that has been observed in several large studie@. Genetic differences among trial populations is one of several possible factors that may account for these surprising variations.
In mice, resistance to early growth of M. bovis/EXG is controlled by a single, dominant autosomal gene named Beg'. The same locus also controls innate resistance and susceptibility to M. lepraemuriu&, M. intracellulare9 and M. avium'O and is presently believed to be identical to the Lsh and 1~ loci, which control innate resistance to infection with L. donovani and S. typhimurium, respectively". This article focuses on the results obtained using mycobacteria as infectious agents but it must be stressed that strategies similar to those described here have been used for the study of the 1~ and Lsh genes. The conclusions and hypotheses about how, when and where the host resistance locus might be expressed have been suggested by workers from several laboratoriesi2.
It is now well established that the Beg gene is expressed by mature tissue macrophages. Experiments in viuo have shown that resistance to mycobacterial infection is inde-