The host immune response to Mycobacterium tuberculosis determining protection or disease progression

Tuberculosis (TB) remains a global health issue and leading cause of death. Understanding the immune response to Mycobacterium tuberculosis infection is critical to advance TB control. Although immune factors involved in protection against TB have long been identified, these cannot predict the efficacy of TB vaccines, nor which individuals will control the infection or progress to active TB disease. This is especially challenging given the complexity of M. tuberculosis infection states and the breadth of TB disease severities, which is increasingly apparent from basic, clinical and translational research. Here, we discuss the evolving spectrum of M. tuberculosis infection outcomes and TB disease, how the host immune response determines and unfolds across this spectrum and how the natural diversity of M. tuberculosis contributes to this complexity. Integration of these new concepts with fast-evolving systems immunology approaches holds great potential to inform the design of novel strategies to control TB.