Role Played by the Programmed Death-1-Programmed Death Ligand Pathway during Innate Immunity against Mycobacterium tuberculosis

ALVAREZ IB; PASQUINELLI V; JURADO JO; ABBATE E; MUSELLA RM; DE LA BARRERA S; GARCÍA VE

JOURNAL OF INFECTIOUS DISEASES

UNIV CHICAGO PRESS

Año: 2010 vol. 202 p. 524 - 532

0022-1899

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 g (IFN-g), 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-g expression on NK cells was observed. Moreover,blockade of the PD-1 pathway markedly augmented lytic degranulation and IFN-g production of NK cells against M. tuberculosis. Furthermore, PD-1+ NK cells displayed a diminished IFN-g mean fluorescence intensity,denoting the relevance of PD-1 on IFN-g regulation. Together, we described a novel inhibitory role played by PD-1:PD-L interactions in innate immunity in tuberculosis.