Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Lucknow, Uttar Pradesh, India.
J Med Virol. 2022 Mar;94(3):869-877. doi: 10.1002/jmv.27405. Epub 2021 Oct 26.
Balanced immune regulation is crucial for recognizing an invading pathogen, its killing, and elimination. Toll-like receptors (TLRs) are the key regulators of the innate immune system. It helps in identifying between self and nonself-molecule and eventually eliminates the nonself. Endosomal TLR, mainly TLR3, TLR7, TLR8, and membrane-bound TLR4, has a role in the induction of cytokine storms. TLR7/8 recognizes the ssRNA SARS-COV-2 and when it replicates to dsRNA, it is recognized by TLR3 and drives the TRIF-mediated inflammatory signaling like NF-κB, MAPK. Such signaling leads to significant transcription and translation of pro-inflammatory genes, releasing inflammatory molecules into the systemic circulation, causing an imbalance in the system. So, whenever an imbalance occurs, a surge in the pro-inflammatory mediators is observed in the blood, including cytokines like interleukin (IL)-2, IL-4, IL-6, IL-1β, IL-8, interferon (IFN)-γ, tumor necrosis factor (TNF)-α. IL-6 and IL-1β are one of the driving factors for bringing the cytokine storm into the systemic circulation, which migrates into the other organs, causing multiple organ failures leading to the death of the individual with severe illness.
平衡的免疫调节对于识别入侵病原体、杀死和消除病原体至关重要。 Toll 样受体 (TLR) 是先天免疫系统的关键调节剂。它有助于识别自我和非自我分子，最终消除非自我。内体 TLR，主要是 TLR3、TLR7、TLR8 和膜结合 TLR4，在细胞因子风暴的诱导中发挥作用。TLR7/8 识别 ssRNA SARS-COV-2，当它复制为 dsRNA 时，被 TLR3 识别，并通过 TRIF 介导的炎症信号如 NF-κB、MAPK 驱动。这种信号导致促炎基因的大量转录和翻译，将炎症分子释放到全身循环中，导致系统失衡。因此，每当发生失衡时，血液中促炎介质的水平会急剧上升，包括细胞因子如白细胞介素 (IL)-2、IL-4、IL-6、IL-1β、IL-8、干扰素 (IFN)-γ、肿瘤坏死因子 (TNF)-α。IL-6 和 IL-1β 是将细胞因子风暴带入全身循环的驱动因素之一，它迁移到其他器官，导致多器官衰竭，导致重病患者死亡。
