Role played by the programmed death-1-programmed death ligand pathway during innate immunity against Mycobacterium tuberculosis.
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.
Alvarez
Ivana B
IB
Department of Biological Chemistry, University of Buenos Aires, School of Sciences, Buenos Aires, Argentina.
Pasquinelli
Virginia
V
Jurado
Javier O
JO
Abbate
Eduardo
E
Musella
Rosa M
RM
de la Barrera
Silvia S
SS
García
Verónica E
VE
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
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