Murine Model of Tuberculosis. In vitro and in vivo Study

Animal models that mimic the whole spectrum of susceptibility and resistance of human populations to tuberculosis would be useful for studying pathogenesis of tuberculosis, mechanisms of the host defense, and for testing prospective prophylactic and therapeutic tuberculosis vaccines and drugs. Inbred mouse strains are broadly and successfully used to model human tuberculosis and study mechanisms of host-mycobacteria interaction. Here we consider numerous aspects of murine models of tuberculosis. We analyze the course of tuberculosis depending on route and dosage of mycobacterial infection, and discuss the conformity of these approaches to the natural route of human infection. The advantage of the mouse model is provided by the availability of hundreds of inbred strains with different genetic background. It allows a genetic analysis of the mouse susceptibility/resistance to tuberculosis. Mouse strains with specific properties such as congenic, recombinant, recombinant inbred, recombinant congenic, mutant and usage of whole genome screening led to mapping loci controlling these traits. Transgenic mouse strains with gene insertion or targeted mutation (knock-out of a gene) are very effective tools for studying the role of specific genes controlling the anti-tuberculosis immunity. Mice with knock-out genes for cytokines, chemokines, cell subpopulations, cell receptors, and enzymes are broadly used to identify the mechanisms of tuberculosis control. In this review we examine a mouse model for anti-tuberculosis vaccine and drug testing. In addition, we present some important phenomena of tuberculosis immunity - latent tuberculosis/reactivation and immunological memory to tuberculosis.