Toll-like receptors in sepsis-associated cytokine storm and their endogenous negative regulators as future immunomodulatory targets.
Toll-like receptors in sepsis-associated cytokine storm and their endogenous negative regulators as future immunomodulatory targets.
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DOI：
10.1016/j.intimp.2020.107087
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发表时间：
2020-12
影响因子：
5.6
通讯作者：
Kumar V
中科院分区：
文献类型：
--
作者：
Kumar V
脓毒症在全球范围内感染了超过4890万人，其中1970万人死亡。细胞因子风暴在脓毒症中起着重要作用，沿着严重的COVID-19。TLR信号通路在产生细胞因子风暴中起着至关重要的作用。TLR信号传导的内源性负调节因子对调节细胞因子风暴至关重要。细胞因子风暴在各种全身性急性感染期间产生，包括脓毒症和当前称为COVID-19（严重）的大流行，导致破坏性炎症状况，包括多器官衰竭或多器官功能障碍综合征（MODS）和患者死亡。Toll样受体（TLR）是免疫细胞和非免疫细胞（包括神经元）表达的主要模式识别受体（PRRs）之一，在产生细胞因子风暴中起着至关重要的作用。它们识别微生物相关的分子模式（MAMP，由病原体表达）和损伤或死亡相关的分子模式（DAMP;由受损/死亡的宿主细胞释放和/或表达）。识别MAMP和DAMP后，TLR激活下游信号通路，释放几种促炎介质[细胞因子、趋化因子、干扰素以及活性氧和氮物质（ROS或RNS）]，引起急性炎症，旨在控制病原体并修复损伤。由于宿主的遗传组成和/或由于其逃避机制导致的病原体的持续存在而引起的过度反应的诱导可能导致称为脓毒症的严重全身性炎症性病症，以响应细胞因子风暴和器官功能障碍的产生。TLR诱导的炎症反应的激活与诱导几种负反馈机制紧密相连，这些负反馈机制发挥作用以结束反应并维持免疫稳态。本文综述了TLR信号在脓毒症相关细胞因子风暴发生中的重要性，并讨论了TLR信号通路的各种宿主源性内源性负调节因子。这个问题是非常重要的，因为有大量的基因和过程涉及这些负反馈机制。这些分子和机制可以用于开发用于细胞因子风暴相关疾病的新型治疗药物，包括败血症，严重的COVID-19和其他炎性疾病，其中TLR信号传导起着重要作用。
Sepsis infects more than 48.9 million people world-wide, with 19.7 million deaths. Cytokine storm plays a significant role in sepsis, along with severe COVID-19. TLR signaling pathways plays a crucial role in generating the cytokine storm. Endogenous negative regulators of TLR signaling are crucial to regulate cytokine storm. Cytokine storm generates during various systemic acute infections, including sepsis and current pandemic called COVID-19 (severe) causing devastating inflammatory conditions, which include multi-organ failure or multi-organ dysfunction syndrome (MODS) and death of the patient. Toll-like receptors (TLRs) are one of the major pattern recognition receptors (PRRs) expressed by immune cells as well as non-immune cells, including neurons, which play a crucial role in generating cytokine storm. They recognize microbial-associated molecular patterns (MAMPs, expressed by pathogens) and damage or death-associate molecular patterns (DAMPs; released and/expressed by damaged/killed host cells). Upon recognition of MAMPs and DAMPs, TLRs activate downstream signaling pathways releasing several pro-inflammatory mediators [cytokines, chemokines, interferons, and reactive oxygen and nitrogen species (ROS or RNS)], which cause acute inflammation meant to control the pathogen and repair the damage. Induction of an exaggerated response due to genetic makeup of the host and/or persistence of the pathogen due to its evasion mechanisms may lead to severe systemic inflammatory condition called sepsis in response to the generation of cytokine storm and organ dysfunction. The activation of TLR-induced inflammatory response is hardwired to the induction of several negative feedback mechanisms that come into play to conclude the response and maintain immune homeostasis. This state-of-the-art review describes the importance of TLR signaling in the onset of the sepsis-associated cytokine storm and discusses various host-derived endogenous negative regulators of TLR signaling pathways. The subject is very important as there is a vast array of genes and processes implicated in these negative feedback mechanisms. These molecules and mechanisms can be targeted for developing novel therapeutic drugs for cytokine storm-associated diseases, including sepsis, severe COVID-19, and other inflammatory diseases, where TLR-signaling plays a significant role.
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影响因子：
4.4
作者：
Benko, Szilvia;Magalhaes, Joao G.;Girardin, Stephen E.
通讯作者：
Girardin, Stephen E.
影响因子：
5.5
作者：
Abram, Clare L.;Lowell, Clifford A.
通讯作者：
Lowell, Clifford A.
DOI：
10.4049/jimmunol.1102157
发表时间：
2012-03-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Bauerfeld CP;Rastogi R;Pirockinaite G;Lee I;Hüttemann M;Monks B;Birnbaum MJ;Franchi L;Nuñez G;Samavati L
通讯作者：
Samavati L
影响因子：
3.5
作者：
Bashirova, AA;Markelov, ML;Frolova, EI
通讯作者：
Frolova, EI
影响因子：
8.8
作者：
Angus, D C;Linde-Zwirble, W T;Pinsky, M R
通讯作者：
Pinsky, M R