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P2X7 blockade in mice with advanced tuberculosis recapitulated in many aspects the disease in P2X7-deficient mice. P2X7-directed therapy reduced body weight loss and the development of inflammatory and necrotic lung lesions, as well as delayed mycobacterial growth. Lower TNF-\u03b1 production by lung cells and a substantial reduction in the lung GR-1<jats:sup>+<\/jats:sup>myeloid cell population were observed after P2X7 inhibition. The effector CD4<jats:sup>+<\/jats:sup>T cell population also decreased, but IFN-\u03b3 production by lung cells increased. The presence of a large population with characteristics of myeloid dendritic cells, as well as the increase in IL-6 production by lung cells, also indicate a qualitative improvement in the pulmonary immune response due to P2X7 inhibition. 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