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PD-1/PD-L pathway inhibits M.tb-specific CD4(+) T-cell functions and phagocytosis of macrophages in active tuberculosis

The role of the PD-1/PD-L pathway in a murine model of tuberculosis remains controversial regarding viral infections and clinical tuberculosis. We conducted a case-control study to investigate the modulating role and mechanism of the PD-1/PD-L pathway in patients with active tuberculosis. Fifty-nine...

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Autores principales: Shen, Lei, Gao, Yan, Liu, Yuanyuan, Zhang, Bingyan, Liu, Qianqian, Wu, Jing, Fan, Lin, Ou, Qinfang, Zhang, Wenhong, Shao, Lingyun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5141449/
https://www.ncbi.nlm.nih.gov/pubmed/27924827
http://dx.doi.org/10.1038/srep38362
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author Shen, Lei
Gao, Yan
Liu, Yuanyuan
Zhang, Bingyan
Liu, Qianqian
Wu, Jing
Fan, Lin
Ou, Qinfang
Zhang, Wenhong
Shao, Lingyun
author_facet Shen, Lei
Gao, Yan
Liu, Yuanyuan
Zhang, Bingyan
Liu, Qianqian
Wu, Jing
Fan, Lin
Ou, Qinfang
Zhang, Wenhong
Shao, Lingyun
author_sort Shen, Lei
collection PubMed
description The role of the PD-1/PD-L pathway in a murine model of tuberculosis remains controversial regarding viral infections and clinical tuberculosis. We conducted a case-control study to investigate the modulating role and mechanism of the PD-1/PD-L pathway in patients with active tuberculosis. Fifty-nine participants, including 43 active tuberculosis (ATB) patients and 16 healthy controls (HC), were enrolled. Cell surface staining and flow cytometry were used to detect the expressions of PD-1 and its ligands on T cells and monocytes. Intracellular cytokine staining was used to determine the PPD-specific IFN-γ-secreting T-cell proportion. CD4(+) T-cell proliferation and macrophage functions were investigated in the presence or absence of PD-1/PD-L pathway blockade. Proportions of both PD-1(+)CD4(+) and PD-L1(+)CD4(+) T cells in ATB patients were more significantly increased than in the HC group (P = 0.0112 and P = 0.0141, respectively). The expressions of PD-1, PD-L1, and PD-L2 on CD14(+) monocytes in ATB patients were much higher than those in the HC group (P = 0.0016, P = 0.0001, and P = 0.0088, respectively). Blockade of PD-1 could significantly enhance CD4(+) T-cell proliferation (P = 0.0433). Phagocytosis and intracellular killing activity of macrophages increased significantly with PD-1/PD-L pathway blockade. In conclusion, the PD-1/PD-L pathway inhibits not only M.tb-specific CD4(+) T-cell-mediated immunity but also innate immunity.
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spelling pubmed-51414492016-12-16 PD-1/PD-L pathway inhibits M.tb-specific CD4(+) T-cell functions and phagocytosis of macrophages in active tuberculosis Shen, Lei Gao, Yan Liu, Yuanyuan Zhang, Bingyan Liu, Qianqian Wu, Jing Fan, Lin Ou, Qinfang Zhang, Wenhong Shao, Lingyun Sci Rep Article The role of the PD-1/PD-L pathway in a murine model of tuberculosis remains controversial regarding viral infections and clinical tuberculosis. We conducted a case-control study to investigate the modulating role and mechanism of the PD-1/PD-L pathway in patients with active tuberculosis. Fifty-nine participants, including 43 active tuberculosis (ATB) patients and 16 healthy controls (HC), were enrolled. Cell surface staining and flow cytometry were used to detect the expressions of PD-1 and its ligands on T cells and monocytes. Intracellular cytokine staining was used to determine the PPD-specific IFN-γ-secreting T-cell proportion. CD4(+) T-cell proliferation and macrophage functions were investigated in the presence or absence of PD-1/PD-L pathway blockade. Proportions of both PD-1(+)CD4(+) and PD-L1(+)CD4(+) T cells in ATB patients were more significantly increased than in the HC group (P = 0.0112 and P = 0.0141, respectively). The expressions of PD-1, PD-L1, and PD-L2 on CD14(+) monocytes in ATB patients were much higher than those in the HC group (P = 0.0016, P = 0.0001, and P = 0.0088, respectively). Blockade of PD-1 could significantly enhance CD4(+) T-cell proliferation (P = 0.0433). Phagocytosis and intracellular killing activity of macrophages increased significantly with PD-1/PD-L pathway blockade. In conclusion, the PD-1/PD-L pathway inhibits not only M.tb-specific CD4(+) T-cell-mediated immunity but also innate immunity. Nature Publishing Group 2016-12-07 /pmc/articles/PMC5141449/ /pubmed/27924827 http://dx.doi.org/10.1038/srep38362 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Shen, Lei
Gao, Yan
Liu, Yuanyuan
Zhang, Bingyan
Liu, Qianqian
Wu, Jing
Fan, Lin
Ou, Qinfang
Zhang, Wenhong
Shao, Lingyun
PD-1/PD-L pathway inhibits M.tb-specific CD4(+) T-cell functions and phagocytosis of macrophages in active tuberculosis
title PD-1/PD-L pathway inhibits M.tb-specific CD4(+) T-cell functions and phagocytosis of macrophages in active tuberculosis
title_full PD-1/PD-L pathway inhibits M.tb-specific CD4(+) T-cell functions and phagocytosis of macrophages in active tuberculosis
title_fullStr PD-1/PD-L pathway inhibits M.tb-specific CD4(+) T-cell functions and phagocytosis of macrophages in active tuberculosis
title_full_unstemmed PD-1/PD-L pathway inhibits M.tb-specific CD4(+) T-cell functions and phagocytosis of macrophages in active tuberculosis
title_short PD-1/PD-L pathway inhibits M.tb-specific CD4(+) T-cell functions and phagocytosis of macrophages in active tuberculosis
title_sort pd-1/pd-l pathway inhibits m.tb-specific cd4(+) t-cell functions and phagocytosis of macrophages in active tuberculosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5141449/
https://www.ncbi.nlm.nih.gov/pubmed/27924827
http://dx.doi.org/10.1038/srep38362
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