Experimental murine TB: understanding the disease and advancing interventions

Tuberculosis (TB) continues to cause extensive morbidity and high death tolls worldwide. The failure to control TB, which most frequently affects the lung, is partly due to incomplete understanding of disease pathogenesis. Tractable disease models, including experimental murine infection, have already contributed to identification of immune checkpoints in TB and are indispensable for testing new therapies or vaccines. While acknowledging limitations of the murine models, for instance with regard to TB lesion diversity, rational selection of specific mouse models for selected purposes holds promise for the TB research. Diverse inbred and outbred strains, as well as genetically modified and collaborative cross-lines allow high-throughput screens and high-resolution investigations. Moreover, systems approaches and utilization of murine models mimicking primary progressive TB enable identification of immune correlates of protection and determinants of immunopathology. Our studies in TB-susceptible inbred mice have unveiled immunological mechanisms underlying detrimental roles of type I interferons in TB and emphasized importance of the early immune events for the control of pulmonary inflammation. The murine experimental TB models should be collectively harnessed for advancing effective interventions for TB.