Methyl jasmonate promotes host defense by activating autophagy during Mycobacterium tuberculosis infection

Jasmonates are a class of plant hormones that play multiple roles in plant growth, development, stress responses, and antimicrobial activity. However, their role in antimicrobial responses in mammalian cells and in vivo, particularly against Mycobacterium tuberculosis (Mtb), remains unclear. Tuberculosis remains a global challenge in human health, particularly with the rise of multidrug-resistant strains. Thus, exploring novel therapeutic agents is urgently warranted. In this study, we investigated the antimicrobial effects of methyl jasmonate (MeJA) against Mtb to evaluate its potential as a novel host-directed therapy agent.

MeJA did not exhibit direct antimycobacterial effects; however, it induced antimicrobial responses in macrophages and in vivo against Mtb, including multidrug-resistant strains. During infection, MeJA significantly reduced the expression of proinflammatory cytokines and chemokines in both macrophages and lung tissues. Furthermore, MeJA treatment inhibits the AKT-MTOR axis, leading to increased expression of autophagy-related and lysosomal genes by promoting nuclear translocation of transcription factor EB in macrophages during M. tuberculosis infection. MeJA robustly activated autophagy, thereby enhancing phagosomal maturation and promoting antimicrobial responses.

Together, our results provide valuable insights into the potential of MeJA for developing novel, plant-derived strategies to combat mycobacterial infections, highlighting its role in enhancing host defense mechanisms by ameliorating pathological inflammation and activating autophagy.