Mycobacterium tuberculosis (Mtb) employs distinct strategies to circumvent host immune responses during the infection process. Various Mtb cell-wall associated and secretory proteins are known to play a critical role in the orchestration of host innate immune responses through modulation of signaling pathways. Mtb genome encodes for 23 (EsxA-EsxW) proteins belonging to the ESAT-6 like family; however, most of them are functionally unknown. Here, we show that Mtb EsxL induces tumor necrosis factor-alpha (TNF-α) production by activating nuclear translocation of nuclear factor-κB (NF-κB) via interaction with Toll-like Receptor 2 (TLR2). Blocking or silencing of TLR2 abrogated nuclear translocation of NF-kB and TNF-α production. Treatment with recombinant purified EsxL (rEsxL) activated mitogen-activated protein kinase (MAPK) pathway by inducing the phosphorylation of extracellular signal-regulated kinase (ERK) and p38 kinase (p38) pathways. At the same time, inhibition of ERK and p38 down-regulated the expression of TNF-α in rEsxL exposed murine macrophages. Besides TNF-α, EsxL also induced the production of IL-6 proinflammatory cytokine. Taken together, these results suggest that EsxL is able to induce TNF-α secretion via TLR2 through activation of NF-κB and MAPK signaling. This study will help in deducing therapeutic strategies for better control of the disease.

结核分枝杆菌（Mtb）在感染过程中采用了独特的策略来规避宿主的免疫反应。已知各种Mtb细胞壁相关蛋白和分泌蛋白通过信号通路的调控在宿主先天免疫应答的编排中起关键作用。Mtb基因组编码23种（EsxA-EsxW）蛋白质，属于ESAT-6样家族；但是，大多数功能在功能上是未知的。在这里，我们显示Mtb EsxL通过与Toll样受体2（TLR2）相互作用激活核因子-κB（NF-κB）的核易位，从而诱导肿瘤坏死因子-α（TNF-α）的产生。TLR2的阻滞或沉默消除了NF-kB和TNF-α产生的核易位。通过诱导细胞外信号调节激酶（ERK）和p38激酶（p38）途径的磷酸化，用重组纯化的EsxL（rEsxL）活化的促丝裂原活化蛋白激酶（MAPK）途径进行治疗。同时，ERK和p38的抑制下调了rEsxL暴露的鼠巨噬细胞中TNF-α的表达。除TNF-α外，EsxL还诱导IL-6促炎细胞因子的产生。综上所述，这些结果表明，EsxL能够通过激活NF-κB和MAPK信号传导，通过TLR2诱导TNF-α分泌。这项研究将有助于推导更好地控制疾病的治疗策略。除TNF-α外，EsxL还诱导IL-6促炎细胞因子的产生。综上所述，这些结果表明，EsxL能够通过激活NF-κB和MAPK信号传导，通过TLR2诱导TNF-α分泌。这项研究将有助于推导更好地控制疾病的治疗策略。除TNF-α外，EsxL还诱导IL-6促炎细胞因子的产生。综上所述，这些结果表明，EsxL能够通过激活NF-κB和MAPK信号传导，通过TLR2诱导TNF-α分泌。这项研究将有助于推导更好地控制疾病的治疗策略。