Abstract
Tuberculosis (TB), which is caused by Mycobacterium tuberculosis (Mtb), remains the leading cause of death worldwide from a single infectious pathogen. Mtb is a paradigmatic intracellular pathogen that primarily invades the lungs after host inhalation of bacteria-containing droplets via the airway. However, the majority of Mtb-exposed individuals can spontaneously control the infection by virtue of a robust immune defense system. The mucosal barriers of the respiratory tract shape the first-line defense against Mtb through various mucosal immune responses. After arriving at the alveoli, the surviving mycobacteria further encounter a set of host innate immune cells that exert multiple cellular bactericidal functions. Adaptive immunity, predominantly mediated by a range of different T cell and B cell subsets, is subsequently activated and participates in host anti-mycobacterial defense. During Mtb infection, host bactericidal immune responses are exquisitely adjusted and balanced by multifaceted mechanisms, including genetic and epigenetic regulation, metabolic regulation and neuroendocrine regulation, which are indispensable for maintaining host immune efficiency and avoiding excessive tissue injury. A better understanding of the integrated and equilibrated host immune defense system against Mtb will contribute to the development of rational TB treatment regimens especially novel host-directed therapeutics.