Modulation of Microtubule Dynamics Affects Brucella abortus Intracellular Survival, Pathogen-Containing Vacuole Maturation, and Pro-inflammatory Cytokine Production in Infected Macrophages.
Modulation of Microtubule Dynamics Affects Brucella abortus Intracellular Survival, Pathogen-Containing Vacuole Maturation, and Pro-inflammatory Cytokine Production in Infected Macrophages.
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DOI：
10.3389/fmicb.2017.02217
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发表时间：
2017
影响因子：
5.2
通讯作者：
Oliveira SC
中科院分区：
文献类型：
--
作者：
Alves-Silva J;Tavares IP;Guimarães ES;Costa Franco MM;Figueiredo BC;Marques JT;Splitter G;Oliveira SC
微管(MT)细胞骨架调节与免疫系统相关的几个细胞过程。例如，MTS介导的错综复杂的细胞内转运负责天然免疫的囊泡受体及其适配蛋白的正确定位。在本研究中，我们用诺可达唑诱导流产布鲁氏菌感染的骨髓巨噬细胞MT解聚，并用紫杉醇或重组(R)TIR(Toll/IL-1受体)结构域蛋白(TcpB)诱导MT稳定。在细胞处理后，我们评估了它们对病原体细胞内复制和存活以及促炎细胞因子产生的影响。首先，我们观察到含有布鲁氏菌的囊泡(BCV)的细胞内运输和成熟受到MTS网络部分失稳或稳定的影响。早期BCV的典型标志物LAMP-1在小剂量诺康唑或紫杉醇和不同剂量的rTcpB存在下，即使在感染后24小时仍保留在晚期BCV中。其次，显微镜和集落形成单位分析显示，与未处理的细胞相比，低剂量诺康唑或紫杉醇和rTcpB处理的感染巨噬细胞的细菌载量增加。第三，先天免疫反应也受到MT动力学干扰的影响。诺可达唑的MT解聚减少了感染巨噬细胞中IL-12的产生。相反，rTcpB处理的细胞增加了感染细胞中IL-12和IL-1β的分泌。综上所述，这些发现表明MTS的调节影响流产杆菌致病的几个关键步骤，包括BCV成熟、细胞内存活和感染巨噬细胞分泌IL-12。
The microtubule (MT) cytoskeleton regulates several cellular processes related to the immune system. For instance, an intricate intracellular transport mediated by MTs is responsible for the proper localization of vesicular receptors of innate immunity and its adaptor proteins. In the present study, we used nocodazole to induce MTs depolymerization and paclitaxel or recombinant (r) TIR (Toll/interleukin-1 receptor) domain containing protein (TcpB) to induce MT stabilization in bone marrow-derived macrophages infected with Brucella abortus. Following treatment of the cells, we evaluated their effects on pathogen intracellular replication and survival, and in pro-inflammatory cytokine production. First, we observed that intracellular trafficking and maturation of Brucella-containing vesicles (BCVs) is affected by partial destabilization or stabilization of the MTs network. A typical marker of early BCVs, LAMP-1, is retained in late BCVs even 24 h after infection in the presence of low doses of nocodazole or paclitaxel and in the presence of different amounts of rTcpB. Second, microscopy and colony forming unit analysis revealed that bacterial load was increased in infected macrophages treated with lower doses of nocodazole or paclitaxel and with rTcpB compared to untreated cells. Third, innate immune responses were also affected by disturbing MT dynamics. MT depolymerization by nocodazole reduced IL-12 production in infected macrophages. Conversely, rTcpB-treated cells augmented IL-12 and IL-1β secretion in infected cells. In summary, these findings demonstrate that modulation of MTs affects several crucial steps of B. abortus pathogenesis, including BCV maturation, intracellular survival and IL-12 secretion in infected macrophages.
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影响因子：
30.3
作者：
Starr T;Child R;Wehrly TD;Hansen B;Hwang S;López-Otin C;Virgin HW;Celli J
通讯作者：
Celli J
影响因子：
3.1
作者：
de Souza Filho, Job Alves;Martins, Vicente de Paulo;Oliveira, Sergio Costa
通讯作者：
Oliveira, Sergio Costa
影响因子：
4.5
作者：
Starr, Tregei;Ng, Tony W.;Celli, Jean
通讯作者：
Celli, Jean
影响因子：
3.4
作者：
Comerci, DJ;Martínez-Lorenzo, MJ;Ugalde, RA
通讯作者：
Ugalde, RA
影响因子：
6.7
作者：
Salcedo, Suzana P.;Marchesini, Maria Ines;Lelouard, Hugues;Fugier, Emilie;Jolly, Gilles;Balor, Stephanie;Muller, Alexandre;Lapaque, Nicolas;Demaria, Olivier;Alexopoulou, Lena;Comerci, Diego J.;Ugalde, Rodolfo A.;Pierre, Philippe;Gorvel, Jean-Pierre
通讯作者：
Gorvel, Jean-Pierre