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 γ (IFN-γ), and their functions are regulated by activating and inhibitory receptors. Programmed death-1 (...

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Detalles Bibliográficos
Autores: Alvarez, Ivana Belén, Pasquinelli, Virginia, Jurado, Javier Oscar, Abbate, Pablo Eduardo, Musella, Rosa María, de la Barrera, Silvia Susana, García, Verónica Edith
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2010
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/66505
Acceso en línea:http://hdl.handle.net/11336/66505
Access Level:acceso abierto
Palabra clave:Tuberculosis
Innate Immunity
Costimulation
Nk Cells
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
Descripción
Sumario: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 γ (IFN-γ), 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:PDL1/ 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-γ expression on NK cells was observed. Moreover, blockade of the PD-1 pathway markedly augmented lytic degranulation and IFN-γ production of NK cells against M. tuberculosis. Furthermore, PD-1+ NK cells displayed a diminished IFN-γ mean fluorescence intensity, denoting the relevance of PD-1 on IFN-γ regulation. Together, we described a novel inhibitory role played by PD-1:PD-L interactions in innate immunity in tuberculosis. © 2010 by the Infectious Diseases Society of America.