Susceptibility to Mycobacterium tuberculosis: lessons from inbred strains of mice

Inbred strains of mice exhibit varied patterns of susceptibility following infection with virulent Mycobacterium tuberculosis. Susceptible mice have progressive fulminate disease resulting in their premature death; in contrast, resistant mice are able to control bacterial replication, limit lung injury and survive longer. The use of these mouse strains in experimental infection has allowed the identification of immunological correlates of protective versus unsuccessful host responses to tuberculosis, and the identification of susceptibility loci by combining classical and molecular genetics. These immunological and genetic features that distinguish susceptible and resistant inbred mouse strains may allow us to better understand susceptibility to tuberculous disease in people. A possible benefit would be the delineation of markers of protective immunity for use in vaccine development. This is a review of recent insights into the genetics and immunology of resistance and susceptibility to virulent M. tuberculosis using genetically intact mice.