Targeting TLR4 Signaling to Blunt Viral-Mediated Acute Lung Injury.
Targeting TLR4 Signaling to Blunt Viral-Mediated Acute Lung Injury.
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DOI：
10.3389/fimmu.2021.705080
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发表时间：
2021
影响因子：
7.3
通讯作者：
Vogel SN
中科院分区：
文献类型：
--
作者：
Shirey KA;Blanco JCG;Vogel SN
呼吸道病毒感染一直是一个长期的全球负担，从季节性复发到意外的大流行。每年因季节性病毒（如流感）而住院治疗的人数可能会有很大波动，这取决于流行毒株以及与用于每年疫苗制剂的预测毒株的一致性，而预测毒株通常并不准确。虽然抗病毒药物可用于对抗流感，但由于感染时间和症状发展与病毒耐药性之间的时间脱节，疗效有限。不受控制的流感感染可导致由病原体相关分子模式（PAMP）或宿主衍生的病原体相关分子模式（DAMP）引发的严重炎症反应，最终通过模式识别受体（PRR）发出信号。总体而言，这些病原体-宿主相互作用导致局部细胞因子风暴，导致急性肺损伤（ALI）或更严重的急性呼吸窘迫综合征（ARDS），伴随全身受累和更严重的危及生命的后果。除了传统的抗病毒治疗外，阻断宿主的先天免疫反应可能提供一种更可行的方法来对抗这些传染性病原体。SARS-CoV-2大流行表明迫切需要新的治疗方法来对抗已经导致全球数百万人死亡的ALI和ARDS。本文将探讨如何拮抗TLR 4信号已有效的实验在改善急性肺损伤和致死性感染的挑战模型引发的不仅是流感，但也由其他急性肺损伤诱导病毒。
Respiratory viral infections have been a long-standing global burden ranging from seasonal recurrences to the unexpected pandemics. The yearly hospitalizations from seasonal viruses such as influenza can fluctuate greatly depending on the circulating strain(s) and the congruency with the predicted strains used for the yearly vaccine formulation, which often are not predicted accurately. While antiviral agents are available against influenza, efficacy is limited due to a temporal disconnect between the time of infection and symptom development and viral resistance. Uncontrolled, influenza infections can lead to a severe inflammatory response initiated by pathogen-associated molecular patterns (PAMPs) or host-derived danger-associated molecular patterns (DAMPs) that ultimately signal through pattern recognition receptors (PRRs). Overall, these pathogen-host interactions result in a local cytokine storm leading to acute lung injury (ALI) or the more severe acute respiratory distress syndrome (ARDS) with concomitant systemic involvement and more severe, life threatening consequences. In addition to traditional antiviral treatments, blocking the host’s innate immune response may provide a more viable approach to combat these infectious pathogens. The SARS-CoV-2 pandemic illustrates a critical need for novel treatments to counteract the ALI and ARDS that has caused the deaths of millions worldwide. This review will examine how antagonizing TLR4 signaling has been effective experimentally in ameliorating ALI and lethal infection in challenge models triggered not only by influenza, but also by other ALI-inducing viruses.
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影响因子：
3.7
作者：
Chen TY;Chen DY;Wen HW;Ou JL;Chiou SS;Chen JM;Wong ML;Hsu WL
通讯作者：
Hsu WL
影响因子：
7.6
作者：
Abdul-Careem, Mohamed F.;Mian, M. Firoz;Ashkar, Ali A.
通讯作者：
Ashkar, Ali A.
影响因子：
4.1
作者：
Byun, Mi Ran;Jeong, Hana;Hong, Jeong-Ho
通讯作者：
Hong, Jeong-Ho
影响因子：
4.4
作者：
Brockwell-Staats C;Webster RG;Webby RJ
通讯作者：
Webby RJ
DOI：
10.1073/pnas.91.25.11811
发表时间：
1994-12-06
影响因子：
11.1
作者：
CLERICI, M;SARIN, A;HENKART, PA
通讯作者：
HENKART, PA