CD157 Confers Host Resistance to <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content> via TLR2-CD157-PKCzeta-Induced Reactive Oxygen Species Production

ABSTRACT 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 prot...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	CD157 Mycobacterium tuberculosis PKCzeta TLR2 reactive oxygen species Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/6f7481f533f041d985548ff9000e8852
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spelling	oai:doaj.org-article:6f7481f533f041d985548ff9000e88522021-11-15T16:22:09ZCD157 Confers Host Resistance to <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content> via TLR2-CD157-PKCzeta-Induced Reactive Oxygen Species Production10.1128/mBio.01949-192150-7511https://doaj.org/article/6f7481f533f041d985548ff9000e88522019-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01949-19https://doaj.org/toc/2150-7511ABSTRACT 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. IMPORTANCE Tuberculosis, a chronic bacterial disease caused by Mycobacterium tuberculosis, remains a major global health problem. CD157, a dual-function receptor and β-NAD+-metabolizing ectoenzyme, promotes cell polarization, regulates chemotaxis induced through the high-affinity fMLP receptor, and controls transendothelial migration. The role of CD157 in TB pathogenesis remains unknown. In this study, we find that both mRNA and protein levels of CD157 are significantly increased in TB. Deficiency of CD157 impaired host defense against M. tuberculosis infection both in vivo and in vitro, which is mediated by an interaction among CD157, TLR2, and PKCzeta. This interaction facilitates M. tuberculosis-induced macrophagic ROS production, which enhances macrophage bactericidal activity. Interestingly, the sCD157 level in plasma is reversibly associated with MDM M. tuberculosis killing activity. By uncovering the role of CD157 in pathogenesis of TB for the first time, our work demonstrated that application of soluble CD157 might be an effective strategy for host-directed therapy against TB.Qianting YangMingfeng LiaoWenfei WangMingxia ZhangQi ChenJiubiao GuoBin PengJian HuangHaiying LiuAyano YahagiXingzhi XuKatsuhiko IshiharaAndrea CooperXinchun ChenYi CaiAmerican Society for MicrobiologyarticleCD157Mycobacterium tuberculosisPKCzetaTLR2reactive oxygen speciesMicrobiologyQR1-502ENmBio, Vol 10, Iss 4 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	CD157 Mycobacterium tuberculosis PKCzeta TLR2 reactive oxygen species Microbiology QR1-502
spellingShingle	CD157 Mycobacterium tuberculosis PKCzeta TLR2 reactive oxygen species Microbiology QR1-502 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 CD157 Confers Host Resistance to <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content> via TLR2-CD157-PKCzeta-Induced Reactive Oxygen Species Production
description	ABSTRACT 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. IMPORTANCE Tuberculosis, a chronic bacterial disease caused by Mycobacterium tuberculosis, remains a major global health problem. CD157, a dual-function receptor and β-NAD+-metabolizing ectoenzyme, promotes cell polarization, regulates chemotaxis induced through the high-affinity fMLP receptor, and controls transendothelial migration. The role of CD157 in TB pathogenesis remains unknown. In this study, we find that both mRNA and protein levels of CD157 are significantly increased in TB. Deficiency of CD157 impaired host defense against M. tuberculosis infection both in vivo and in vitro, which is mediated by an interaction among CD157, TLR2, and PKCzeta. This interaction facilitates M. tuberculosis-induced macrophagic ROS production, which enhances macrophage bactericidal activity. Interestingly, the sCD157 level in plasma is reversibly associated with MDM M. tuberculosis killing activity. By uncovering the role of CD157 in pathogenesis of TB for the first time, our work demonstrated that application of soluble CD157 might be an effective strategy for host-directed therapy against TB.
format	article
author	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
author_facet	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
author_sort	Qianting Yang
title	CD157 Confers Host Resistance to <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content> via TLR2-CD157-PKCzeta-Induced Reactive Oxygen Species Production
title_short	CD157 Confers Host Resistance to <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content> via TLR2-CD157-PKCzeta-Induced Reactive Oxygen Species Production
title_full	CD157 Confers Host Resistance to <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content> via TLR2-CD157-PKCzeta-Induced Reactive Oxygen Species Production
title_fullStr	CD157 Confers Host Resistance to <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content> via TLR2-CD157-PKCzeta-Induced Reactive Oxygen Species Production
title_full_unstemmed	CD157 Confers Host Resistance to <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content> via TLR2-CD157-PKCzeta-Induced Reactive Oxygen Species Production
title_sort	cd157 confers host resistance to <named-content content-type="genus-species">mycobacterium tuberculosis</named-content> via tlr2-cd157-pkczeta-induced reactive oxygen species production
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/6f7481f533f041d985548ff9000e8852
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CD157 Confers Host Resistance to <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content> via TLR2-CD157-PKCzeta-Induced Reactive Oxygen Species Production

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