結(jié)核分枝菌是一種能引發(fā)肺結(jié)核的細(xì)菌,，世界上有1/3的人口被這種細(xì)菌所感染,，基本上每1秒種就有一個(gè)新感染案例，從而造成全球性的健康問題,。如今,，研究人員在6月號(hào)的《自然—免疫學(xué)》（Nature Immunology）期刊上報(bào)告說,，他們發(fā)現(xiàn)結(jié)核分枝菌分泌出的一種蛋白質(zhì)能夠嚴(yán)重抑制早期的免疫反應(yīng)。
以前的研究發(fā)現(xiàn),，結(jié)核分枝細(xì)菌分泌的ESAT-6蛋白質(zhì)與免疫系統(tǒng)對(duì)結(jié)核分枝細(xì)菌的無效反應(yīng)有關(guān),，如今，Joyoti Basu和同事評(píng)估了這種蛋白質(zhì)的功能,。Toll樣受體（TLRs）是機(jī)體通過感知病原微生物體并激活細(xì)胞直接產(chǎn)生免疫防御的天然免疫受體,，Basu等發(fā)現(xiàn)，純化的ESAT-6能阻斷特定的免疫受體蛋白質(zhì)——Toll樣受體的信號(hào),，產(chǎn)生這種機(jī)制的關(guān)鍵是ESAT-6與一種Toll受體——TLR2在巨噬細(xì)胞表面上的特定相互作用,，巨噬細(xì)胞是一種重要的免疫前哨。他們發(fā)現(xiàn),，通過與TLR2的結(jié)合,，ESAT-6誘導(dǎo)出一種關(guān)閉所有Toll樣受體功能的信號(hào)。
研究人員指出,，阻斷ESAT-6與TLR2間的相互作用也許是一種治療肺結(jié)核的潛在方法,，而模擬ESAT-6與TLR2間的相互作用將有助于抑制過度的炎癥反應(yīng)。（生物谷援引科學(xué)時(shí)報(bào)）
原始出處:
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: [email protected]
