TLR4-NOX2 axis regulates the phagocytosis and killing of Mycobacterium tuberculosis by macrophages

BMC Pulmonary Medicine

Research Article

Xiaojing Wang¹  Jingzhu Lv²  Xiaoyan He²  Gabriel T. Kelly³  Ting Wang³  Yin Chen⁴  Zhaohua Wang⁵  Hongtao Wang⁶  Zhongqing Qian⁶ 

[1] Anhui Clinical and Preclinical Key Laboratory of Respiratory Disease, Department of Respiration, First Affiliated Hospital; Bengbu Medical College, 233000, Bengbu, Anhui, China;Department of Biochemistry and Molecular Biology, Bengbu Medical College, 233003, Bengbu, Anhui, China;Department of Medicine, The University of Arizona, P.O. Box 245218, 1656 E. Mabel St, 85724, Tucson, AZ, USA;Department of Pharmacology and Toxicology, The University of Arizona, 85724, Tucson, AZ, USA;Department of Pulmonary Medicine, Bengbu Infectious Disease Hospital, 233003, Bengbu, Anhui, China;Key Laboratory of Anhui Province for Infection and Immunology, Bengbu Medical College, 2600 Donghai Ave, 233003, Bengbu, Anhui, China;

关键词: TB;    TLR;    NOX2;    Phagocytosis;   

DOI  :  10.1186/s12890-017-0517-0

 received in 2017-01-04, accepted in 2017-11-21,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundMacrophages stand at the forefront of both innate and adapted immunity through their capacities to recognize, engulf, and eliminate foreign particles, and to stimulate adapted immune cells. They are also involved in controlling pro- and anti-inflammatory pathways. Macrophage activity against Mycobacterium tuberculosis (M. tuberculosis) has been shown to involve Toll-like receptor (TLR) activation and ROS production. Previous studies have shown that lipopolysaccharide (LPS), through TLR4, could activate macrophages, improve their bactericidal ROS production, and facilitate anti-infective immune responses. We sought to better understand the role of the TLR4-NOX2 axis in macrophage activation during M. tuberculosis infection.MethodsTHP-1 macrophages and PMA primed THP-1 macrophages [THP-1(A)] were treated with LPS and infected by M. tuberculosis. Cells were analyzed by flow cytometry for TLR4 expression, ROS production, phagocytosis, and killing of M. tuberculosis. Western blotting was used to analyze NOX2 expression. Inhibitors of the TLR4-NOX2 pathway were used to assess this pathway’s role in these processes, and their role in LPS activation of macrophages.ResultsWe found that THP1-derived macrophages or PMA primed THP-1 macrophages exhibit higher surface TLR4 levels and increased NOX2 expression levels following LPS treatment. M. tuberculosis infection reduced these levels, but LPS was able to limit the negative effects of M.tb. Additionally, LPS increases THP-1(A) cells’ bactericidal activities including phagocytosis, ROS production, and destruction of M. tuberculosis. Significantly, all of these activities are impaired when TLR4 or NOX2 are inhibited.ConclusionThese studies demonstrate the importance of the TLR4-NOX2 axis in M. tuberculosis elimination by macrophages and may lead to novel therapies for tuberculosis and other bacterial infections.

【 授权许可】

CC BY   
© The Author(s). 2017

【 图 表 】

12864_2016_3353_Article_IEq29.gif