Mycobacterium tuberculosis Zinc Metalloprotease-1 Assists Mycobacterial Dissemination in Zebrafish.
Mycobacterium tuberculosis Zinc Metalloprotease-1 Assists Mycobacterial Dissemination in Zebrafish.
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DOI：
10.3389/fmicb.2016.01347
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发表时间：
2016
影响因子：
5.2
通讯作者：
Banerjee S
中科院分区：
文献类型：
--
作者：
Vemula MH;Medisetti R;Ganji R;Jakkala K;Sankati S;Chatti K;Banerjee S
结核分枝杆菌(M.tb)的锌金属蛋白酶-1(ZMP1)是引起结核杆菌(TB)的一种毒力因子，参与了炎性小体失活和吞噬小体成熟停滞。我们早些时候报道，Zmp1在肉芽肿样应激条件下分泌，诱导Th2细胞因子微环境，从患者血清中高滴度的抗Zmp1抗体可以看出，Zmp1在结核病患者中具有高度的免疫原性。在这项研究中，我们破译了Zmp1在分枝杆菌传播中的一个新的生理作用。用500nM和1μM的重组ZMP1(RZMP1)外源处理THP-1细胞，可导致细胞死亡。除诱导肿瘤坏死因子α、IL-6和IL-1β的分泌外，还可诱导趋化趋化因子单核细胞趋化蛋白-1、巨噬细胞趋化因子-1β和IL-8的释放，提示其可能在细胞迁移和分枝杆菌扩散中发挥作用。缝隙关闭和博伊登小室实验证实了这一点，ZMP1处理的CHO或THP-1细胞显示∼使细胞迁移比未处理的细胞增加2倍。此外，斑马鱼-M.采用海洋寄主-病原体模型研究分枝杆菌在体内的传播。TD-标记海洋分支杆菌的番茄(TDM.当注射rZmp1时，与未经处理的对照鱼相比，rZmp1以剂量依赖的方式增加了从注射部位向尾部区域的扩散。综上所述，我们认为ZMP1是一种多方面的蛋白，当分枝杆菌在肉芽肿中释放时，可能会导致坏死性细胞损伤，并通过周围感染的巨噬细胞释放趋化因子，吸引新的免疫细胞，进而可能导致新的细胞感染，从而帮助分枝杆菌的扩散。
Zinc metalloprotease-1 (Zmp1) from Mycobacterium tuberculosis (M.tb), the tuberculosis (TB) causing bacillus, is a virulence factor involved in inflammasome inactivation and phagosome maturation arrest. We earlier reported that Zmp1 was secreted under granuloma-like stress conditions, induced Th2 cytokine microenvironment and was highly immunogenic in TB patients as evident from high anti-Zmp1 antibody titers in their sera. In this study, we deciphered a new physiological role of Zmp1 in mycobacterial dissemination. Exogenous treatment of THP-1 cells with 500 nM and 1 μM of recombinant Zmp1 (rZmp1) resulted in necrotic cell death. Apart from inducing secretion of necrotic cytokines, TNFα, IL-6, and IL-1β, it also induced the release of chemotactic chemokines, MCP-1, MIP-1β, and IL-8, suggesting its likely function in cell migration and mycobacterial dissemination. This was confirmed by Gap closure and Boyden chamber assays, where Zmp1 treated CHO or THP-1 cells showed ∼2 fold increased cell migration compared to the untreated cells. Additionally, Zebrafish-M. marinum based host–pathogen model was used to study mycobacterial dissemination in vivo. Td-Tomato labeled M. marinum (TdM. marinum) when injected with rZmp1 showed increased dissemination to tail region from the site of injection as compared to the untreated control fish in a dose-dependent manner. Summing up these observations along with the earlier reports, we propose that Zmp1, a multi-faceted protein, when released by mycobacteria in granuloma, may lead to necrotic cell damage and release of chemotactic chemokines by surrounding infected macrophages, attracting new immune cells, which in turn may lead to fresh cellular infections, thus assisting mycobacterial dissemination.
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影响因子：
3.4
作者：
Calamita, H;Ko, C;Bishai, WR
通讯作者：
Bishai, WR
DOI：
10.1084/jem.20080767
发表时间：
2008-11-24
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Chen M;Divangahi M;Gan H;Shin DS;Hong S;Lee DM;Serhan CN;Behar SM;Remold HG
通讯作者：
Remold HG
影响因子：
3.7
作者：
Butler RE;Brodin P;Jang J;Jang MS;Robertson BD;Gicquel B;Stewart GR
通讯作者：
Stewart GR
影响因子：
3.1
作者：
BOOTH, BA;BOESMANFINKELSTEIN, M;FINKELSTEIN, RA
通讯作者：
FINKELSTEIN, RA
影响因子：
1.2
作者：
Benard, Erica L.;van der Sar, Astrid M.;Meijer, Annemarie H.
通讯作者：
Meijer, Annemarie H.