Interleukin-12 production by human monocytes infected with Mycobacterium tuberculosis: role of phagocytosis.

摘要: Mycobacterium tuberculosis and its antigens are potent inducers of cytokine expression by mononuclear phagocytes. In this study, the ability live M. to stimulate interleukin-12 (IL-12) human monocytes was examined. Monocytes were purified from peripheral blood cells adherence either infected with or exposed soluble protein (purified derivative [PPD]). Live (10(6) 10(7) CFU/ml) a stimulus for (IL-12). By using reverse transcription-PCR, p40 mRNA detected at 3 h, peaked 6 12 decayed baseline levels 18 24 h following infection. Bioactive IL-12 (p70) measured phytohemagglutinin blast proliferation assay confirmed results. contrast, PPD concentrations known readily induce IL-1 tumor necrosis factor alpha (10 100 microg/ml) poor expression. The different efficiencies bacilli in part due requirement phagocytosis. Induction response reduced cytochalasin D. Furthermore, phagocytosis dead inert 2-micron-diameter polystyrene beads induced mRNA. 0.5-micron-diameter beads, which can enter through pinocytosis, did not Functionally, enhanced PPD-stimulated IFN-gamma production CD4+ T-cell-mediated cytotoxicity healthy tuberculin-positive donors but less enhancement when antigen. These results suggest that is upregulated as early phagocytes cellular events associated themselves signal production. released macrophages turn further upregulate tuberculosis-specific T-cell effector function.