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 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: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-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-gmean 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. Tuberculous pleurisy, one of the most common man-ifestations of extrapulmonary tuberculosis, is a severe delayed-type hypersensitivity reaction against the rup