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CD157 Confers Host Resistance to Mycobacterium tuberculosis via TLR2-CD157-PKCzeta-Induced Reactive Oxygen Species Production

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journal contribution
posted on 21.05.2020, 11:15 by Qianting Yang, Mingfeng Liao, Wenfei Wang, Mingxia Zhang, Qi Chen, Jiubiao Guo, Bin Peng, Jian Huang, Haiying Liu, Ayano Yahagi, Xingzhi Xu, Katsuhiko Ishihara, Andrea Cooper, Xinchun Chen, Yi Cai
Recruitment of monocytes to the infection site is critical for host resistance against Mycobacterium tuberculosis. CD157 has a crucial role in neutrophil and monocyte transendothelial migration and adhesion, but its role in tuberculosis (TB) is unclear. Here, we show that both mRNA and protein levels of Cd157 are significantly increased during M. tuberculosis infection. Deficiency of Cd157 impaired host response to M. tuberculosis infection by increasing bacterial burden and inflammation in the lung in the murine TB model. In vitro experiments show that the bactericidal ability was compromised in Cd157 knockout (KO) macrophages, which was due to impaired M. tuberculosis-induced reactive oxygen species (ROS) production. We further reveal that CD157 interacts with TLR2 and PKCzeta and facilitates M. tuberculosis-induced ROS production in Cd157 KO macrophages, which resulted in enhanced M. tuberculosis killing. For the clinic aspect, we observe that the expression of CD157 decreases after effective anti-TB chemotherapy. CD157 is specifically increased in pleural fluid in tuberculous pleurisy patients compared to pneumonia and lung cancer patients. Interestingly, the levels of soluble CD157 (sCD157) correlate with human peripheral monocyte-derived macrophage bactericidal activity. Exogenous application of sCD157 could compensate for macrophage bactericidal ability and restore ROS production. In conclusion, we have identified a novel protective immune function of CD157 during M. tuberculosis infection via TLR2-dependent ROS production. Application of sCD157 might be an effective strategy for host-directed therapy against TB in those with insufficient CD157 production.

Funding

The study was supported by Natural Science Foundation of China (81525016, 81772145, 81770013, 31500727, and 81671984), National Science and Technology Major Project (2017ZX10201301), Science and Technology Project of Shenzhen (JCYJ20160427184123851 and JCYJ20170412101048337), Jin Qi team of Sanming Project of Medicine in Shenzhen (SZSM201412001), and JSPS KAKENHI (17K08798).

History

Citation

mBio 10:e01949-19

Author affiliation

Leicester Tuberculosis Research Group

Version

VoR (Version of Record)

Published in

mBio

Volume

10

Issue

4

Publisher

American Society for Microbiology

eissn

2150-7511

Acceptance date

29/07/2019

Copyright date

2019

Language

English