1. Role Played by the Programmed Death-1-Programmed Death Ligand Pathway during Innate Immunity against Mycobacterium tuberculosis.
- Author
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Alvarez, Ivana B., Pasquinelli, Virginia, Jurado, Javier O., Abbate, Eduardo, Musella, Rosa M., de la Barrera, Silvia S., and Garcia, Veronica E.
- Subjects
NATURAL immunity ,MYCOBACTERIUM tuberculosis ,PLEURISY ,TUBERCULOSIS mortality ,LYMPHOCYTES ,KILLER cells ,INTERFERONS ,DEATH receptors ,FLUORESCENCE - Abstract
Tuberculous pleurisy allows the study of specific cells at the site of 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: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-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. [ABSTRACT FROM AUTHOR]- Published
- 2010
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