LPS restores protective immunity in macrophages against Mycobacterium tuberculosis via autophagy. (August 2020)

• Record Type: Journal Article
• Authors: Fang, Fang; Ge, Qing; Li, Rui; Lv, Jingzhu; Zhang, Yao; Feng, Anlin; Kelly, Gabriel T.; Wang, Hongtao; Wang, Xiaojing; Song, Chuanwang; Wang, Ting; Qian, Zhongqing
• Is Part Of: Molecular immunology. Volume 124(2020:Aug.)
• Page Start: 18
• Page End: 24
• Publication Date: 2020-08
• Subjects: Mycobacterium tuberculosis -- Autophagy -- IL-12 -- IFN-γ; Immunochemistry -- Periodicals; Molecular biology -- Periodicals; Immunochemistry -- Periodicals; Allergy and Immunology -- Periodicals; Molecular Biology -- Periodicals; Immunochimie -- Périodiques; Biologie moléculaire -- Périodiques; Immunochemistry; Molecular biology; Periodicals; Electronic journals; 571.96
• DOI: 10.1016/j.molimm.2020.05.001
• Languages: English
• ISSNs: 0161-5890

Abstract

Highlights: TB patient blood transcriptomes indicate M. tuberculosis affects autophagy. Rapamycin and LPS induce autophagy in TB infected macrophages. LPS restores IL-12 synthesis in TB infected macrophages. 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.