The Mouse Model of Tuberculosis: Uses and Abuses

The mouse provides a flexible tool to probe the interactions between the immune system and the slow growing and persistent bacterium, Mycobacterium tuberculosis (Mtb). Removal of specific cells or molecules from mice demonstrates the causal connection between these elements and control of Mtb; these connections are also seen in humans. Systems genetics, with single-cell and spatial technologies, have transformed the working model of immunity to tuberculosis (TB) in mice and humans; determining the spatiotemporal role of immune elements in immunity will allow development of targeted and precise interventions to control TB. As cure from TB is associated with lifelong health consequences, we need to also use mouse models to understand the health impact of the immune response to TB. Use of the mouse model requires precise experimental design and cautious interpretation. Rational incorporation of mouse-derived data into our working model of TB will refine our understanding of the natural history of TB worldwide.