title: Role played by the programmed death-1-programmed death ligand pathway during innate immunity against Mycobacterium tuberculosis.
abstract: Tuberculous pleurisy allows the study of specific cells at the site of Mycobacterium tuberculosis infection. Among pleural lymphocytes, natural killer (NK) cells are a major source of interferon gamma (IFN-gamma), and their functions are regulated by activating and inhibitory receptors. Programmed death-1 (PD-1), programmed death ligand 1 (PD-L1), and programmed death ligand 2 (PD-L2) are recognized inhibitory receptors in adaptive immunity, but their role during innate immunity remains poorly understood. We investigated the PD-1:PD-L1/PD-L2 pathway on NK cell effector functions in peripheral blood and pleural fluid from patients with tuberculosis. M. tuberculosis stimulation significantly up-regulated PD-1, PD-L1, and PD-L2 levels on NK cells. Interestingly, a direct correlation between PD-1 and IFN-gamma expression on NK cells was observed. Moreover, blockade of the PD-1 pathway markedly augmented lytic degranulation and IFN-gamma production of NK cells against M. tuberculosis. Furthermore, PD-1(+) NK cells displayed a diminished IFN-gamma mean fluorescence intensity, denoting the relevance of PD-1 on IFN-gamma regulation. Together, we described a novel inhibitory role played by PD-1:PD-L interactions in innate immunity in tuberculosis.
authors.affiliation: Department of Biological Chemistry, University of Buenos Aires, School of Sciences, Buenos Aires, Argentina.
authors.forename: Ivana B
authors.initials: IB
authors.lastname: Alvarez
authors.forename: Virginia
authors.initials: V
authors.lastname: Pasquinelli
authors.forename: Javier O
authors.initials: JO
authors.lastname: Jurado
authors.forename: Eduardo
authors.initials: E
authors.lastname: Abbate
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Musella
authors.forename: Silvia S
authors.initials: SS
authors.lastname: de la Barrera
authors.forename: Verónica E
authors.initials: VE
authors.lastname: García
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000276:immunology*; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000276:immunology*; D060890:B7-H1 Antigen; D001769:Blood / Q000276:immunology; D020869:Gene Expression Profiling; D006801:Humans; D007113:Immunity, Innate; D036341:Intercellular Signaling Peptides and Proteins / Q000276:immunology; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D010994:Pleura / Q000276:immunology; D061027:Programmed Cell Death 1 Ligand 2 Protein; D061026:Programmed Cell Death 1 Receptor; D014376:Tuberculosis / Q000276:immunology* / Q000473:pathology*; D015854:Up-Regulation
chemical_list: D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D036341:Intercellular Signaling Peptides and Proteins; C105992:PDCD1 protein, human; C556977:PDCD1LG2 protein, human; D061027:Programmed Cell Death 1 Ligand 2 Protein; D061026:Programmed Cell Death 1 Receptor; D007371:Interferon-gamma