期刊
JOURNAL OF INFECTION
卷 80, 期 6, 页码 E19-E26出版社
W B SAUNDERS CO LTD
DOI: 10.1016/j.jinf.2020.03.003
关键词
Tuberculosis; Host-directed therapy; Ibrutinib; Autophagy
资金
- Thirteen-Fifth Mega-Scientific Project on Prevention and Treatment of AIDS, Viral Hepatitis and Other Infectious Diseases [2017ZX10201301]
- National Natural Science Foundation of China [81800010, 81525016, 81671984]
- Provincial Natural Sciencice Foundation of Guandong [2018A030310642, 2020A1515010415]
- Guangdong Provincial Science and Technology Program [2019B030301009]
- Shenzhen Science and Technology Innovation Foundation [JCYJ20180305163440858]
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. (C) 2020 The British Infection Association. Published by Elsevier Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据