2. Academic Validation
  3. Ibrutinib suppresses intracellular mycobacterium tuberculosis growth by inducing macrophage autophagy

Ibrutinib suppresses intracellular mycobacterium tuberculosis growth by inducing macrophage autophagy

  • J Infect. 2020 Jun;80(6):e19-e26. doi: 10.1016/j.jinf.2020.03.003.
Yunlong Hu 1,  Zhihua Wen 2,  Song Liu 3,  Yi Cai 1,  Jiubiao Guo 1,  Yuzhong Xu 1,  Dachuan Lin 1,  Jialou Zhu 1,  Dechang Li 2,  Xinchun Chen 4
Affiliations

Affiliations

  • 1 Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Department of Pathogen Biology, School of Medicine, Shenzhen University, Shenzhen 518055, China.
  • 2 Yuebei Second People's Hospital, Shaoguan 512028, China.
  • 3 Clinical Medical Research Center, The Second Clinical Medical College of Jinan University (Shenzhen People's Hospital), Shenzhen 518020, China.
  • 4 Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Department of Pathogen Biology, School of Medicine, Shenzhen University, Shenzhen 518055, China. Electronic address: chenxinchun@szu.edu.cn.
PMID: 32171871 DOI: 10.1016/j.jinf.2020.03.003
Abstract

Tuberculosis (TB) is a major cause of morbidity and mortality worldwide. The host-directed therapy is a promising strategy for TB treatment that synergize with anti-TB treatment drugs. In this study, we found that the anti-chronic lymphocytic leukemia drug, ibrutinib, inhibited the growth of intracellular Mtb in human macrophages. Mechanisms studies showed that ibrutinib treatment significantly decreased p62 and increased LC3b proteins in Mtb infected macrophages. In addition, ibrutinib increased LC3b colocalization with intracellular Mtb and auto-lysosome fusion. Furthermore, inhibition of Autophagy by using siRNA targeting Atg7 abolished the effect of ibrutinib-mediated suppression of intracellular Mtb. Next, we found that ibrutinib induced Autophagy was through inhibition of Btk/Akt/mTOR pathway. Finally, we confirmed that ibrutinib treatment significantly reduced Mtb load in mediastinal node and spleen of Mtb infected mice. In conclusion, our data suggest that ibrutinib is a potential host-directed therapy candidate against TB.

Keywords

Autophagy; Host-directed therapy; Ibrutinib; Tuberculosis.

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