School of Biotechnology, Faculty of Science, Banaras Hindu University, Varanasi 221005, India.
Vaccine. 2012 Aug 24;30(39):5748-54. doi: 10.1016/j.vaccine.2012.07.002. Epub 2012 Jul 13.
Mycobacterium indicus pranii (MIP) is a non-pathogenic strain of mycobacterium and has been used as a vaccine against tuberculosis and leprosy. Here, we investigated the role of different pattern recognition receptors in the recognition of heat-killed MIP by macrophages. Treatment of macrophages with MIP caused upregulation of pro-inflammatory cytokines (like TNFα and IL-1β) which was mediated through both TLR2 and NOD2, as revealed by our knockdown and/or knockout studies. Mechanistically, MIP-induced macrophage activation was shown to result in NF-κB activation and drastically abrogated by MyD88 deficiency, suggesting its regulation via an MyD88-dependent, NF-κB pathway. Interestingly, the IFN-inducible cytokine, CXCL10, which is known target of the TRIF-dependent TLR pathway was found to be upregulated in response to MIP but, in an MyD88-dependent manner. Collectively, these results demonstrate macrophages to recognize and respond to MIP through a TLR2, NOD2 and an MyD88-dependent pathway. However, further studies should clarify whether additional TLR-dependent or -independent pathways also exist in regulating the full spectrum of MIP action on macrophage activation.
印度分枝杆菌（MIP）是一种非致病性分枝杆菌菌株，已被用作结核病和麻风病的疫苗。在这里，我们研究了不同模式识别受体在巨噬细胞识别热灭活 MIP 中的作用。用 MIP 处理巨噬细胞会导致促炎细胞因子（如 TNFα 和 IL-1β）的上调，这是通过我们的敲低和/或敲除研究揭示的，通过 TLR2 和 NOD2 介导。在机制上，MIP 诱导的巨噬细胞活化导致 NF-κB 激活，而 MyD88 缺乏则严重阻断，表明其通过 MyD88 依赖性 NF-κB 途径进行调节。有趣的是，IFN 诱导的细胞因子 CXCL10 是 TRIF 依赖性 TLR 途径的已知靶标，研究发现它对 MIP 的反应呈上调，但以 MyD88 依赖性方式。总之，这些结果表明巨噬细胞通过 TLR2、NOD2 和 MyD88 依赖性途径识别和响应 MIP。然而，进一步的研究应该阐明是否存在其他 TLR 依赖性或非依赖性途径来调节 MIP 对巨噬细胞活化的全面作用。
