LPS restores protective immunity in macrophages against Mycobacterium tuberculosis via autophagy

Fang Fang, Qing Ge, Rui Li, Jingzhu Lv, Yao Zhang, Anlin Feng, Gabriel T. Kelly, Hongtao Wang, Xiaojing Wang, Chuanwang Song, Ting Wang, Zhongqing Qian

Research output: Contribution to journalArticle

Abstract

Autophagy has been identified as an important immune regulatory mechanism. Recent studies have linked macrophage autophagy with innate immune responses against Mycobacterium tuberculosis (M. tuberculosis), which can survive within macrophages by blocking fusion of the phagosome with lysosomes. These findings suggest that autophagy is a regulatable cellular mechanism of M. tuberculosis defense in macrophages. Transcriptomic profiles in human blood in TB patients suggest that M. tuberculosis affects autophagy related pathways. In order to better understand the role of macrophage autophagy in enhancing protective immunity against M. tuberculosis, in this study, we investigate the effects of the autophagy activators rapamycin and LPS in macrophage autophagy and immunity against M. tuberculosis. We confirm that rapamycin and LPS induce autophagy in M. tuberculosis infected THP-1-derived macrophages or PMA primed THP-1 macrophages [THP-1(A)]. LPS restores M. tuberculosis-inhibited IL-12 synthesis and secretion in THP-1(A) cells via autophagy. Similarly, autophagy activators increase IL-12 synthesis and secretion in THP-1(A) cells. These studies demonstrate the importance of autophagy in M. tuberculosis elimination in macrophages and may lead to novel therapies for tuberculosis and other bacterial infections.

Original languageEnglish (US)
Pages (from-to)18-24
Number of pages7
JournalMolecular Immunology
Volume124
DOIs
StatePublished - Aug 2020

Keywords

  • Autophagy
  • IFN-γ
  • IL-12
  • Mycobacterium tuberculosis

ASJC Scopus subject areas

  • Immunology
  • Molecular Biology

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  • Cite this

    Fang, F., Ge, Q., Li, R., Lv, J., Zhang, Y., Feng, A., Kelly, G. T., Wang, H., Wang, X., Song, C., Wang, T., & Qian, Z. (2020). LPS restores protective immunity in macrophages against Mycobacterium tuberculosis via autophagy. Molecular Immunology, 124, 18-24. https://doi.org/10.1016/j.molimm.2020.05.001