Mycobacterium tuberculosis (Mtb) is a major causal pathogen of human tuberculosis (TB), which is a serious health burden worldwide. The demand for the development of an innovative therapeutic strategy to treat TB is high due to drug-resistant forms of TB. Autophagy is a cell-autonomous host defense mechanism by which intracytoplasmic cargos can be delivered and then destroyed in lysosomes. Previous studies have reported that autophagy-activating agents and small molecules may be beneficial in restricting intracellular Mtb infection, even with multidrug-resistant Mtb strains. Recent studies have revealed the essential roles of host nuclear receptors (NRs) in the activation of the host defense through antibacterial autophagy against Mtb infection. In particular, we discuss the function of estrogen-related receptor (ERR) α and peroxisome proliferator-activated receptor (PPAR) α in autophagy regulation to improve host defenses against Mtb infection. Despite promising findings relating to the antitubercular effects of various agents, our understanding of the molecular mechanism by which autophagy-activating agents suppress intracellular Mtb in vitro and in vivo is lacking. An improved understanding of the antibacterial autophagic mechanisms in the innate host defense will eventually lead to the development of new therapeutic strategies for human TB.
Therapies that promote intracellular digestion of microbes could prove a valuable addition to antibiotic weapons against tuberculosis. Mycobacterium tuberculosis (Mtb) establishes itself within immune cells, and employs a variety of tricks to protect itself as it sickens its host. Researchers led by Eun-Kyeong Jo at Chungnam National University, Daejeon, South Korea, have reviewed efforts to defeat this pathogen by jump-starting a cellular ‘recycling’ pathway called autophagy. Autophagy helps cells break down both biomolecules aggregates and potential invaders, but Mtb can elude such digestion. Jo and colleagues highlight antimycobacterial agents that can potentially render Mtb vulnerable to autophagy, as well as promising cellular targets that may allow researchers to access this process. For example, evidence suggests that agents that activate a regulatory protein such as ERRα or PPARα could stimulate cellular degradation of Mtb.