Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, 7284University of Washington, USA.
Innate Immun. 2021 Oct;27(7-8):503-513. doi: 10.1177/17534259211051364. Epub 2021 Nov 20.
COVID-19 is both a viral illness and a disease of immunopathology. Proximal events within the innate immune system drive the balance between deleterious inflammation and viral clearance. We hypothesize that a divergence between the generation of excessive inflammation through over activation of the TLR associated myeloid differentiation primary response (MyD88) pathway relative to the TIR-domain-containing adaptor-inducing IFN-β (TRIF) pathway plays a key role in COVID-19 severity. Both viral elements and damage associated host molecules act as TLR ligands in this process. In this review, we detail the mechanism for this imbalance in COVID-19 based on available evidence, and we discuss how modulation of critical elements may be important in reducing severity of disease.
COVID-19 既是一种病毒性疾病，也是一种免疫病理学疾病。先天免疫系统中的近端事件驱动着有害炎症和病毒清除之间的平衡。我们假设，通过与 TIR 结构域包含衔接子诱导 IFN-β（TRIF）途径相比，TLR 相关髓样分化初级反应（MyD88）途径的过度激活导致的过度炎症的产生出现分歧，在 COVID-19 的严重程度中发挥关键作用。在这个过程中，病毒成分和与宿主相关的损伤分子都充当 TLR 配体。在这篇综述中，我们根据现有证据详细阐述了 COVID-19 中这种失衡的机制，并讨论了调节关键因素如何可能有助于降低疾病的严重程度。
