Mast Cell and Eosinophil Activation Are Associated With COVID-19 and TLR-Mediated Viral Inflammation: Implications for an Anti-Siglec-8 Antibody.
Mast Cell and Eosinophil Activation Are Associated With COVID-19 and TLR-Mediated Viral Inflammation: Implications for an Anti-Siglec-8 Antibody.
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DOI：
10.3389/fimmu.2021.650331
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发表时间：
2021
影响因子：
7.3
通讯作者：
Youngblood BA
中科院分区：
文献类型：
--
作者：
Gebremeskel S;Schanin J;Coyle KM;Butuci M;Luu T;Brock EC;Xu A;Wong A;Leung J;Korver W;Morin RD;Schleimer RP;Bochner BS;Youngblood BA
由SARS-CoV-2感染引起的2019冠状病毒病（COVID-19）代表了全球健康危机。通过模式识别受体激活免疫细胞被认为是COVID-19中出现的过度炎症反应的驱动因素。然而，我们对SARS-CoV-2的特异性免疫反应的理解仍然有限。肥大细胞（MC）和嗜酸性粒细胞是在许多炎症反应中起致病作用的先天性免疫细胞。在这里，我们报告了MC衍生的蛋白酶和嗜酸性粒细胞相关介质在COVID-19患者血清和肺组织中升高。体外病毒敏感toll样受体的刺激和体内合成病毒RNA的施用诱导了炎症过度的特征，包括细胞因子升高、免疫细胞气道浸润和MC蛋白酶产生-由选择性抑制MC和消耗嗜酸性粒细胞的抗Siglec-8单克隆抗体抑制的效应。类似地，抗Siglec-8治疗降低了呼吸道病毒感染模型中的疾病严重程度和气道炎症。这些结果表明MC和嗜酸性粒细胞活化与COVID-19炎症相关，并且抗Siglec-8抗体是用于减轻病毒感染期间过度炎症的潜在治疗方法。
Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 infection represents a global health crisis. Immune cell activation via pattern recognition receptors has been implicated as a driver of the hyperinflammatory response seen in COVID-19. However, our understanding of the specific immune responses to SARS-CoV-2 remains limited. Mast cells (MCs) and eosinophils are innate immune cells that play pathogenic roles in many inflammatory responses. Here we report MC-derived proteases and eosinophil-associated mediators are elevated in COVID-19 patient sera and lung tissues. Stimulation of viral-sensing toll-like receptors in vitro and administration of synthetic viral RNA in vivo induced features of hyperinflammation, including cytokine elevation, immune cell airway infiltration, and MC-protease production—effects suppressed by an anti-Siglec-8 monoclonal antibody which selectively inhibits MCs and depletes eosinophils. Similarly, anti-Siglec-8 treatment reduced disease severity and airway inflammation in a respiratory viral infection model. These results suggest that MC and eosinophil activation are associated with COVID-19 inflammation and anti-Siglec-8 antibodies are a potential therapeutic approach for attenuating excessive inflammation during viral infections.
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