title: PD-1/PD-L pathway inhibits M.tb-specific CD4+T-cell functions and phagocytosis of macrophages in active tuberculosis.
abstract: 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.
authors.affiliation: Department of Thoracic Intensive Care Unit, Shanghai Pulmonary Hospital, Tongji University, Shanghai, 200433, China.|Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, 200040, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Shen
authors.affiliation: Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, 200040, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, 200040, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, 200040, China.
authors.forename: Bingyan
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, 200040, China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, 200040, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.affiliation: Clinic and Research Center of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University, Shanghai, 200433, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Fan
authors.affiliation: Department of Pulmonary Diseases, Wuxi Infectious Diseases Hospital, Wuxi, 214005, China.
authors.forename: Qinfang
authors.initials: Q
authors.lastname: Ou
authors.affiliation: Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, 200040, China.|Key Laboratory of Medical Molecular Virology, Ministry of Education and Health, Shanghai Medical College, and Institutes of Biomedical Science, Fudan University, Shanghai, 200032, China.
authors.forename: Wenhong
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, 200040, China.
authors.forename: Lingyun
authors.initials: L
authors.lastname: Shao
mesh_terms: D000328:Adult; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000382:microbiology; D016022:Case-Control Studies; D049109:Cell Proliferation; D005260:Female; D005786:Gene Expression Regulation; D054884:Host-Pathogen Interactions; D006801:Humans; D007111:Immunity, Cellular; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000254:growth & development / Q000276:immunology*; D010587:Phagocytosis; D061251:Primary Cell Culture; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000235:genetics / Q000276:immunology* / Q000382:microbiology
chemical_list: D057134:Antibodies, Neutralizing; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D018950:Lipopolysaccharide Receptors; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D007371:Interferon-gamma