Division of Pathophysiology, National Institute of Cholera and Enteric Diseases, P-33, C.I.T. Road, Scheme-XM, Beliaghata, Kolkata 700010, West Bengal, India.
Mol Immunol. 2010 May;47(9):1739-46. doi: 10.1016/j.molimm.2010.03.001. Epub 2010 Mar 27.
The 34 kDa major outer membrane protein (MOMP) of Shigella flexneri 2a induces combinatorial expression of TLR2 and TLR6 on peritoneal macrophages of BALB/c mice. Between the two best-characterized TLRs, to date, TLR2 and TLR4, which are chiefly responsible for recognizing majority of bacterial products, TLR2 alone participates in recognition of 34 kDa MOMP. In addition to TLRs, MOMP enhances the mRNA expression of MyD88 and TRAF6 and induces the nuclear translocation of NF-kappaB as well as activates p38 MAP kinase, suggesting the involvement of these molecules in the mechanism of action of MOMP. 34 kDa MOMP also stimulates macrophages, up regulates the surface expression of MHC-II and B7-1 and enhances the production of different cytokines (such as ILp70, TNF-alpha, Il-6) and chemokines (like MIP-1 alpha, MIP-1 beta and RANTES). The ability of the protein in the activation of macrophages, i.e. the induction of nuclear translocation of NF-kappaB and secretion of cytokines are dependent on TLR2 expression as demonstrated by the lack of response by macrophages pre-treated with inhibitory TLR2 mAb. Moreover, it has been found that MOMP induced regulation of TLR2 gene expression is dependent on NF-kappaB and p38 MAP kinase in murine macrophages for the first time. The MOMP induced cytokines and chemokines profile reflect that the protein has the ability to translate innate towards type-1 adaptive response. In conclusion MOMP recognizes by and activates macrophages which may be an initiating event in the antibacterial host response.
福氏 2a 志贺菌 34kDa 主要外膜蛋白（MOMP）诱导 BALB/c 小鼠腹腔巨噬细胞中 TLR2 和 TLR6 的组合表达。在迄今为止两个研究最透彻的 TLR 中，TLR2 和 TLR4 主要负责识别大多数细菌产物，TLR2 单独参与 34kDa MOMP 的识别。除 TLR 外，MOMP 还增强了 MyD88 和 TRAF6 的 mRNA 表达，并诱导 NF-κB 的核易位以及激活 p38 MAP 激酶，表明这些分子参与了 MOMP 的作用机制。34kDa MOMP 还刺激巨噬细胞，上调 MHC-II 和 B7-1 的表面表达，并增强不同细胞因子（如 ILp70、TNF-α、Il-6）和趋化因子（如 MIP-1α、MIP-1β 和 RANTES）的产生。该蛋白在激活巨噬细胞方面的能力，即诱导 NF-κB 的核易位和细胞因子的分泌，依赖于 TLR2 的表达，如用抑制性 TLR2 mAb 预处理的巨噬细胞无反应所证明。此外，首次发现 MOMP 诱导的 TLR2 基因表达调节依赖于 NF-κB 和 p38 MAP 激酶在小鼠巨噬细胞中。MOMP 诱导的细胞因子和趋化因子谱反映出该蛋白具有将先天反应转化为 1 型适应性反应的能力。总之，MOMP 识别并激活巨噬细胞，这可能是宿主抗菌反应的起始事件。
