结核分枝菌是一种能引发肺结核的细菌，世界上有1/3的人口被这种细菌所感染，基本上每1秒种就有一个新感染案例，从而造成全球性的健康问题。如今，研究人员在6月号的《自然—免疫学》（Nature Immunology）期刊上报告说，他们发现结核分枝菌分泌出的一种蛋白质能够严重抑制早期的免疫反应。
以前的研究发现，结核分枝细菌分泌的ESAT-6蛋白质与免疫系统对结核分枝细菌的无效反应有关，如今，Joyoti Basu和同事评估了这种蛋白质的功能。Toll样受体（TLRs）是机体通过感知病原微生物体并激活细胞直接产生免疫防御的天然免疫受体，Basu等发现，纯化的ESAT-6能阻断特定的免疫受体蛋白质——Toll样受体的信号，产生这种机制的关键是ESAT-6与一种Toll受体——TLR2在巨噬细胞表面上的特定相互作用，巨噬细胞是一种重要的免疫前哨。他们发现，通过与TLR2的结合，ESAT-6诱导出一种关闭所有Toll样受体功能的信号。
研究人员指出，阻断ESAT-6与TLR2间的相互作用也许是一种治疗肺结核的潜在方法，而模拟ESAT-6与TLR2间的相互作用将有助于抑制过度的炎症反应。（生物谷援引科学时报）
原始出处:
Nature Immunology 8, 610 - 618 (2007)
Published online: 7 May 2007 | doi:10.1038/ni1468
Direct extracellular interaction between the early secreted antigen ESAT-6 of Mycobacterium tuberculosis and TLR2 inhibits TLR signaling in macrophages
Sushil Kumar Pathak1, Sanchita Basu1, Kunal Kumar Basu1, Anirban Banerjee1, Shresh Pathak1, Asima Bhattacharyya1,3, Tsuneyasu Kaisho2, Manikuntala Kundu1 & Joyoti Basu1
Abstract
Expression of early secreted antigenic target protein 6 (ESAT-6) by Mycobacterium tuberculosis is associated with lower innate immune responses to infection. Here we show that ESAT-6 inhibited activation of transcription factor NF-B and interferon-regulatory factors (IRFs) after Toll-like receptor (TLR) signaling; inhibition of TLR signaling by ESAT-6 required the kinase Akt. Direct binding of ESAT-6 to TLR2 activated Akt and prevented interaction between the adaptor MyD88 and 'downstream' kinase IRAK4, thus abrogating NF-B activation. The six carboxy-terminal amino acid residues of ESAT-6 were required and sufficient for the TLR2-mediated inhibitory effect. A critical function for the carboxy-terminal peptide of ESAT-6 in restricting MyD88-dependent TLR signaling emphasizes the possibility that mimetic inhibitory peptides could be used to restrict innate immune responses in situations in which prolonged TLR signaling has deleterious effects.
Bose Institute, Department of Chemistry, Kolkata 700 009, India.
Laboratory for Host Defense, RIKEN Research Center for Allergy and Immunology, Tsurumi-ku, Yokohama City, Kanagawa 230-0045, Japan.
Present address: Department of Internal Medicine, University of Virginia, Charlottesville, Virginia 22908, USA.
Correspondence to: Joyoti Basu1 e-mail: joyoti@vsnl.com
