结核病是严重危害人类健康的重要疾病，其病原菌结核分枝杆菌感染机体后，巨噬细胞通过产生细胞因子TNF-α和IL-6对其发挥关键免疫效应。但结核分枝杆菌对巨噬细胞存在免疫抑制现象，其机制尚不明确。我们前期研究发现：用结核分枝杆菌分泌的Rv2346c蛋白刺激小鼠巨噬细胞后，巨噬细胞分泌TNF-α和IL-6水平以及对结核分枝杆菌的吞噬功能显著下降，且细胞中NF-κB p65基因mRNA水平显著下降；此外，Rv2346c蛋白刺激巨噬细胞后miR-99b及miR-155表达水平显著上升，p38 MAPK磷酸化水平也显著增高。据此，我们拟通过体内外研究证实如下机制：结核分枝杆菌感染巨噬细胞后，Rv2346c蛋白活化p38 MAPK信号分子，上调miR-99b及miRNA-155的表达，后者再靶向抑制NF-κB p65基因，进而抑制细胞因子TNF-α及IL-6的分泌，从而对巨噬细胞产生免疫抑制效应。

Tuberculosis is an important disease harming seriously to human health, pathogen of which is Mycobacterium tuberculosis. After M.tb infects the body, macrophages of the host exert the key immune effect on it through producing cytokines TNF-α and IL-6. However, M.tb could immunosuppress the macrophages and its mechanism remained unclear. It is found in our previous studies that: when stimulated using the Rv2346c protein secreted by M.tb, the murine macrophages displayed significant decreasing ability to secret TNF-α and IL-6 as well as to phagocytize the pathogen, and additionally the expression of mRNA of NF-κB p65 gene declined remarkably; besides, levels of miR-99b and miR-155 expression and the p38 MAPK phosphorylation elevated noteworthily. On this ground, we attempt to confirm the following mechanism via experiments in vivo and in vitro: after M.tb infect the macrophages, Rv2346c protein would activate the signal molecule p38 MAPK, thus up-regulating expression of miR-99b and miRNA-155, which would then targeting-inhibit the NF-κB gene and thereby reduce secretion of cytokine TNF-α and IL-6, consequently developing an immune-suppressive effect on the macrophages.