PLK2 facilitates Mycobacterium tuberculosis clearance via p38 MAPK-mediated ROS production.

BACKGROUND

Traditional anti-tuberculosis (TB) treatments have limitations. Host-directed therapy (HDT), which boosts the immune response, presents a new treatment approach. This study aimed to identify a new host defense factor against tuberculosis, understand its mechanism, and evaluate its potential as an HDT target.

RESULTS

Polo-like kinase 2 (PLK2) was discovered as a novel host restriction factor that increases during Mycobacterium tuberculosis infection. It limited bacterial survival by activating the p38 MAPK pathway and enhancing reactive oxygen species (ROS) production. Additionally, the histone deacetylase inhibitor trichostatin A (TSA) served as a PLK2 agonist, boosting PLK2 levels and decreasing bacterial load in vitro and in vivo.

CONCLUSION

This study identifies PLK2 as a crucial defense against tuberculosis, working through the p38-ROS axis. Targeting this pathway with TSA shows promise for HDT, offering a new strategy and target for tuberculosis treatment.