Oxidization of TGFβ-activated kinase by MPT53 is required for immunity to Mycobacterium tuberculosis
Oxidization of TGFβ-activated kinase by MPT53 is required for immunity to Mycobacterium tuberculosis
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MPT53 氧化 TGFβ 激活激酶是结核分枝杆菌免疫所必需的
DOI：
10.1038/s41564-019-0436-3
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发表时间：
2019-05
影响因子：
28.3
通讯作者：
Jingjing Ca
中科院分区：
文献类型：
--
作者：
Lin Wang;Zhonghua Liu;Jie Wang;Haipeng Liu;Juehui Wu;Tianqi Tang;Haohao Li;Hua Yang;Lianhua Qin;Dapeng Ma;Jianxia Chen;Feng Liu;Peng Wang;Ruijuan Zheng;Peng Song;Yilong Zhou;Zhenling Cui;Xiangyang Wu;Xiaochen Huang;Haijiao Liang;Shanshan Zhang;Jingjing Ca
结核分枝杆菌(Mtb)来源的成分通常被模式识别受体识别，从而启动一系列先天免疫反应。Mtb的一个显著特征是它们利用不同的VII型分泌系统在其疏水和高度不通透的细胞壁上分泌大量蛋白质，但这些Mtb分泌的蛋白质是否以及如何被宿主免疫系统感知在很大程度上仍不清楚。在这里，我们报道了Mtb的一种分泌型二硫键形成样蛋白MPT53(Rv2878c)，它直接与转化生长因子-β激活蛋白1相互作用，并以不依赖于TLR2或MyD88的方式激活Tak1。MPT53诱导TAK1上C210处二硫键的形成，促进其与TRAF和TAB1的相互作用，从而激活TAK1，诱导促炎细胞因子的表达。此外，MPT53及其二硫键氧化还原酶活性是Mtb通过TAK1诱导宿主炎症反应所必需的。我们的发现为宿主信号蛋白感知结核分枝杆菌感染提供了另一种途径，并可能有利于改进当前的疫苗接种策略。
Mycobacterium tuberculosis (Mtb)-derived components are usually recognized by pattern recognition receptors to initiate a cascade of innate immune responses. One striking characteristic of Mtb is their utilization of different type VII secretion systems to secrete numerous proteins across their hydrophobic and highly impermeable cell walls, but whether and how these Mtb-secreted proteins are sensed by host immune system remains largely unknown. Here, we report that MPT53 (Rv2878c), a secreted disulfide-bond-forming-like protein of Mtb, directly interacts with TGF-β-activated kinase 1 (TAK1) and activates TAK1 in a TLR2- or MyD88-independent manner. MPT53 induces disulfide bond formation at C210on TAK1 to facilitate its interaction with TRAFs and TAB1, thus activating TAK1 to induce the expression of pro-inflammatory cytokines. Furthermore, MPT53 and its disulfide oxidoreductase activity is required for Mtb to induce the host inflammatory responses via TAK1. Our findings provide an alternative pathway for host signalling proteins to sense Mtb infection and may favour the improvement of current vaccination strategies.
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影响因子：
8.7
作者：
Stamm CE;Collins AC;Shiloh MU
通讯作者：
Shiloh MU
影响因子：
30.5
作者：
S. Pathak;Sanchita Basu;Kunal Kumar Basu;A. Banerjee;Shresh Pathak;A. Bhattacharyya;T. Kaisho;M. Kundu;J. Basu
通讯作者：
S. Pathak;Sanchita Basu;Kunal Kumar Basu;A. Banerjee;Shresh Pathak;A. Bhattacharyya;T. Kaisho;M. Kundu;J. Basu
影响因子：
9.1
作者：
Mortaz, Esmaeil;Adcock, Ian M.;Tabarsi, Payam;Masjedi, Mohammad Reza;Mansouri, Davood;Velayati, Ali Akbar;Casanova, Jean-Laurent;Barnes, Peter J.
通讯作者：
Barnes, Peter J.
影响因子：
15.9
作者：
Dorhoi, Anca;Iannaccone, Marco;Kaufmann, Stefan H. E.
通讯作者：
Kaufmann, Stefan H. E.
MicroRNA-27a 通过调节钙相关自噬来控制结核分枝杆菌的细胞内存活
影响因子：
16.6
作者：
Liu F;Chen J;Wang P;Li H;Zhou Y;Liu H;Liu Z;Zheng R;Wang L;Yang H;Cui Z;Wang F;Huang X;Wang J;Sha W;Xiao H;Ge B
通讯作者：
Ge B