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

  • Clin Immunol. 2026 Jun:285:110705. doi: 10.1016/j.clim.2026.110705.
Yuanyuan Liu  1 ,  Liyao Chen  1 ,  Lihan Wang  1 ,  Hui Yang  1 ,  Yu Pang  2 ,  Qiang Li  2 ,  Yongli Guo  3 ,  Jie Lu  4
Affiliations
  • 1. Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China.
  • 2. Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing 101149, China.
  • 3. Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China. Electronic address: [email protected].
  • 4. Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China. Electronic address: [email protected].
PMID: 41962814 DOI: 10.1016/j.clim.2026.110705
Abstract

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.

Keywords
Host-directed therapy; Mycobacterium tuberculosis; PLK2; ROS; TSA; p38 MAPK.
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