Pandemic Influenza Infection Promotes Streptococcus pneumoniae Infiltration, Necrotic Damage, and Proteomic Remodeling in the Heart.
Pandemic Influenza Infection Promotes Streptococcus pneumoniae Infiltration, Necrotic Damage, and Proteomic Remodeling in the Heart.
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大流行性流感感染促进肺炎链球菌浸润、坏死性损伤和心脏蛋白质组重构。
DOI：
10.1128/mbio.03257-21
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发表时间：
2022-02-22
期刊：
影响因子：
6.4
通讯作者：
Gonzalez-Juarbe N
中科院分区：
文献类型：
--
作者：
Platt MP;Lin YH;Wiscovitch-Russo R;Yu Y;Gonzalez-Juarbe N
一个多世纪以来，一直有报道称，原发性流感感染会促进一种致命形式的细菌性肺部疾病的发展。最近，由病毒和细菌引起的肺炎事件与心脏损害直接相关。重要的是，目前尚不清楚病毒-细菌的协同作用是否延伸到肺外器官，如心脏。利用非标记定量蛋白质组学和分子方法，我们报告了甲型流感大流行病毒的初次感染导致肺炎链球菌移位到心肌的增加，导致一般生物学改变。我们还观察到，每一次感染单独导致心脏蛋白质组的变化，这些变化在继发性细菌感染(SBI)模型中加剧。对显著上调的蛋白质进行的基因本体论分析表明，在SBI期间，先天免疫活性、氧化过程和离子稳态的变化都有所增加。免疫印迹证实，除了血管紧张素转换酶2的表达增加外，补体和抗氧化活性也增加。使用人类心肌细胞连续感染的体外模型，我们观察到流感通过促进氧化应激增强细菌毒素诱导的坏死细胞死亡来增强肺炎链球菌的细胞毒性。流感感染增加了促进细菌黏附的受体，如心肌细胞中的聚合免疫球蛋白受体和富含纤维连接蛋白亮氨酸的跨膜蛋白1。最后，程序性坏死(即坏死性下垂)缺陷的小鼠表现出先天免疫反应增强，病毒相关途径减少，并促进了SBI的线粒体功能。提出的结果提供了第一个体内证据，流感感染促进肺炎链球菌的渗透、坏死性损伤和心脏蛋白质组重构。
For over a century, it has been reported that primary influenza infection promotes the development of a lethal form of bacterial pulmonary disease. More recently, pneumonia events caused by both viruses and bacteria have been directly associated with cardiac damage. Importantly, it is not known whether viral-bacterial synergy extends to extrapulmonary organs such as the heart. Using label-free quantitative proteomics and molecular approaches, we report that primary infection with pandemic influenza A virus leads to increased Streptococcus pneumoniae translocation to the myocardium, leading to general biological alterations. We also observed that each infection alone led to proteomic changes in the heart, and these were exacerbated in the secondary bacterial infection (SBI) model. Gene ontology analysis of significantly upregulated proteins showed increased innate immune activity, oxidative processes, and changes to ion homeostasis during SBI. Immunoblots confirmed increased complement and antioxidant activity in addition to increased expression of angiotensin-converting enzyme 2. Using an in vitro model of sequential infection in human cardiomyocytes, we observed that influenza enhances S. pneumoniae cytotoxicity by promoting oxidative stress enhancing bacterial toxin-induced necrotic cell death. Influenza infection was found to increase receptors that promote bacterial adhesion, such as polymeric immunoglobulin receptor and fibronectin leucine-rich transmembrane protein 1 in cardiomyocytes. Finally, mice deficient in programmed necrosis (i.e., necroptosis) showed enhanced innate immune responses, decreased virus-associated pathways, and promotion of mitochondrial function upon SBI. The presented results provide the first in vivo evidence that influenza infection promotes S. pneumoniae infiltration, necrotic damage, and proteomic remodeling of the heart.
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影响因子：
8.8
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
通讯作者：
Orihuela CJ
影响因子：
20.1
作者：
Lin YH;Platt MP;Gilley RP;Brown D;Dube PH;Yu Y;Gonzalez-Juarbe N
通讯作者：
Gonzalez-Juarbe N
DOI：
10.1086/591708
发表时间：
2008-10-01
期刊：
The Journal of infectious diseases
影响因子：
--
作者：
Morens DM;Taubenberger JK;Fauci AS
通讯作者：
Fauci AS
影响因子：
6.4
作者：
Beno, Sarah M.;Riegler, Ashleigh N.;Orihuela, Carlos J.
通讯作者：
Orihuela, Carlos J.
影响因子：
6.4
作者：
Weinberger, Daniel M.;Simonsen, Lone;Viboud, Cecile
通讯作者：
Viboud, Cecile