S. aureus Evades Macrophage Killing through NLRP3-Dependent Effects on Mitochondrial Trafficking.
S. aureus Evades Macrophage Killing through NLRP3-Dependent Effects on Mitochondrial Trafficking.
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DOI：
10.1016/j.celrep.2018.02.027
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发表时间：
2018-02-27
期刊：
影响因子：
8.8
通讯作者：
Sellman BR
中科院分区：
文献类型：
--
作者：
Cohen TS;Boland ML;Boland BB;Takahashi V;Tovchigrechko A;Lee Y;Wilde AD;Mazaitis MJ;Jones-Nelson O;Tkaczyk C;Raja R;Stover CK;Sellman BR
金黄色葡萄球菌呼吸道感染的临床严重程度与α毒素（AT）表达相关。AT激活NLRP 3炎性小体; NLRP 3缺失或AT中和可保护小鼠免受致死性S.金黄色肺炎我们检验了这种保护作用不是由于炎性体依赖性细胞因子（IL-1β/IL-18）减少，而是由于巨噬细胞杀菌功能增加的假设。在体内，AT或NLRP 3的中和改善了细菌清除和存活，而阻断IL-1β/IL-18则没有。在体外使用原代人单核细胞来确定NLRP 3改变细菌杀伤的机制。在用靶向NLRP 3的小干扰RNA（siRNA）处理或用AT-null S.在金黄色葡萄球菌中，线粒体与含细菌的吞噬体共定位。线粒体参与激活caspase-1，这是一个依赖于电子传递链复合物II的过程，靠近吞噬体，促进其酸化。这些数据证明了S.金黄色葡萄球菌将自身与细胞内的抗菌过程隔离。在肺中，α毒素（AT）是S.金黄色葡萄球菌逃避先天免疫反应。Cohen等人证明，NLRP 3炎性小体的AT活化使吞噬细胞杀伤机制的关键组分解偶联，即线粒体与内化细菌解离。没有线粒体与内化细菌的紧密联系，巨噬细胞不能有效地杀死S。金黄色。
Clinical severity of Staphylococcus aureus respiratory infection correlates with alpha toxin (AT) expression. AT activates the NLRP3 inflammasome; deletion of Nlrp3, or AT neutralization, protects mice from lethal S. aureus pneumonia. We tested the hypothesis that this protection is not due to a reduction in inflammasome-dependent cytokines (IL-1β/IL-18) but increased bactericidal function of macrophages. In vivo, neutralization of AT or NLRP3 improved bacterial clearance and survival, while blocking IL-1β/IL-18 did not. Primary human monocytes were used in vitro to determine the mechanism through which NLRP3 alters bacterial killing. In cells treated with small interfering RNA (siRNA) targeting NLRP3 or infected with AT-null S. aureus, mitochondria co-localize with bacterial-containing phagosomes. Mitochondrial engagement activates caspase-1, a process dependent on complex II of the electron transport chain, near the phagosome, promoting its acidification. These data demonstrate a mechanism utilized by S. aureus to sequester itself from antimicrobial processes within the cell. In the lung, alpha toxin (AT) is a primary virulence factor used by S. aureus to evade innate immune responses. Cohen et al. demonstrate that AT activation of the NLRP3 inflammasome uncouples key components of the phagocytic killing machinery, namely, mitochondria dissociate from internalized bacteria. Without close association of mitochondria with internalized bacteria, macrophages are unable to effectively kill S. aureus.
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影响因子：
5.8
作者：
Gu, Zuguang;Eils, Roland;Schlesner, Matthias
通讯作者：
Schlesner, Matthias
DOI：
10.4049/jimmunol.0802367
发表时间：
2009-03-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Bryan NB;Dorfleutner A;Rojanasakul Y;Stehlik C
通讯作者：
Stehlik C
影响因子：
32.4
作者：
Iyer SS;He Q;Janczy JR;Elliott EI;Zhong Z;Olivier AK;Sadler JJ;Knepper-Adrian V;Han R;Qiao L;Eisenbarth SC;Nauseef WM;Cassel SL;Sutterwala FS
通讯作者：
Sutterwala FS
DOI：
10.1073/pnas.1002178107
发表时间：
2010-08-31
影响因子：
11.1
作者：
Kuroda, Junya;Ago, Tetsuro;Sadoshima, Junichi
通讯作者：
Sadoshima, Junichi
影响因子：
64.8
作者：
Chouchani, Edward T.;Pell, Victoria R.;Gaude, Edoardo;Aksentijevic, Dunja;Sundier, Stephanie Y.;Robb, Ellen L.;Logan, Angela;Nadtochiy, Sergiy M.;Ord, Emily N. J.;Smith, Anthony C.;Eyassu, Filmon;Shirley, Rachel;Hu, Chou-Hui;Dare, Anna J.;James, Andrew M.;Rogatti, Sebastian;Hartley, Richard C.;Eaton, Simon;Costa, Ana S. H.;Brookes, Paul S.;Davidson, Sean M.;Duchen, Michael R.;Saeb-Parsy, Kourosh;Shattock, Michael J.;Robinson, Alan J.;Work, Lorraine M.;Frezza, Christian;Krieg, Thomas;Murphy, Michael P.
通讯作者：
Murphy, Michael P.