Influenza-Induced Oxidative Stress Sensitizes Lung Cells to Bacterial-Toxin-Mediated Necroptosis.
Influenza-Induced Oxidative Stress Sensitizes Lung Cells to Bacterial-Toxin-Mediated Necroptosis.
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DOI：
10.1016/j.celrep.2020.108062
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发表时间：
2020-08-25
期刊：
影响因子：
8.8
通讯作者：
Orihuela CJ
中科院分区：
文献类型：
--
作者：
Gonzalez-Juarbe N;Riegler AN;Jureka AS;Gilley RP;Brand JD;Trombley JE;Scott NR;Platt MP;Dube PH;Petit CM;Harrod KS;Orihuela CJ
由甲型流感病毒（IAV）合并和继发细菌感染引起的肺炎的特征是其严重性和高死亡率。以前，我们已经表明，细菌致孔毒素（PFT）介导的坏死性凋亡是细菌性肺炎期间急性肺损伤的关键驱动因素。在这里，我们评估的影响，IAV对PFT诱导的急性肺损伤期间的共同和继发肺炎链球菌（Spn）感染。我们观察到，IAV协同敏化肺上皮细胞的PFT介导的坏死性凋亡在体外和小鼠模型的Spn合并感染和继发感染。无病毒的氧化应激的药理学诱导使细胞对PFT介导的坏死性凋亡敏感。抗氧化剂治疗或抑制坏死性凋亡可降低继发性细菌感染期间的疾病严重程度。我们的研究结果推进了我们对流感合并和继发细菌感染的分子基础的理解，并确定了坏死性凋亡抑制和抗氧化治疗作为潜在的干预策略。Gonzalez-Juarbe等人将坏死性凋亡确定为流感病毒感染后继发性细菌感染（SBI）期间调节疾病严重程度的途径。他们表明，流感病毒诱导的氧化应激是使肺细胞对细菌成孔毒素的促坏死活性敏感所必需的，这为解释SBI期间观察到的坏死提供了一种机制。
Pneumonias caused by influenza A virus (IAV) co- and secondary bacterial infections are characterized by their severity and high mortality rate. Previously, we have shown that bacterial pore-forming toxin (PFT)-mediated necroptosis is a key driver of acute lung injury during bacterial pneumonia. Here, we evaluate the impact of IAV on PFT-induced acute lung injury during co- and secondary Streptococcus pneumoniae (Spn) infection. We observe that IAV synergistically sensitizes lung epithelial cells for PFT-mediated necroptosis in vitro and in murine models of Spn co-infection and secondary infection. Pharmacological induction of oxidative stress without virus sensitizes cells for PFT-mediated necroptosis. Antioxidant treatment or inhibition of necroptosis reduces disease severity during secondary bacterial infection. Our results advance our understanding on the molecular basis of co- and secondary bacterial infection to influenza and identify necroptosis inhibition and antioxidant therapy as potential intervention strategies. Gonzalez-Juarbe et al. identify necroptosis as a pathway modulating disease severity during secondary bacterial infection (SBI) following influenza virus infection. They show that influenza-virus-induced oxidative stress is required to sensitize pulmonary cells to the pro-necroptotic activity of bacterial pore-forming toxins, providing a mechanism to explain the necrosis observed during SBI.
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影响因子：
4.6
作者：
Gonzalez-Juarbe N;Bradley KM;Riegler AN;Reyes LF;Brissac T;Park SS;Restrepo MI;Orihuela CJ
通讯作者：
Orihuela CJ
影响因子：
4.6
作者：
Hoffmann J;Machado D;Terrier O;Pouzol S;Messaoudi M;Basualdo W;Espínola EE;Guillen RM;Rosa-Calatrava M;Picot V;Bénet T;Endtz H;Russomando G;Paranhos-Baccalà G
通讯作者：
Paranhos-Baccalà G
影响因子：
6.4
作者：
McCullers, JA;Bartmess, KC
通讯作者：
Bartmess, KC
影响因子：
8
作者：
Brand, Jeffrey D.;Lazrak, Ahmed;Harrod, Kevin S.
通讯作者：
Harrod, Kevin S.
影响因子：
6.7
作者：
González-Juarbe N;Gilley RP;Hinojosa CA;Bradley KM;Kamei A;Gao G;Dube PH;Bergman MA;Orihuela CJ
通讯作者：
Orihuela CJ