Myeloid dysregulation and therapeutic intervention in COVID-19.
Myeloid dysregulation and therapeutic intervention in COVID-19.
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COVID-19中的骨髓失调和治疗干预。
DOI：
10.1016/j.smim.2021.101524
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发表时间：
2021-06
影响因子：
7.8
通讯作者：
Wang J
中科院分区：
文献类型：
--
作者：
Gu R;Mao T;Lu Q;Tianjiao Su T;Wang J
骨髓细胞反应的失调越来越多地被证明是COVID-19发病的主要机制。与这种疾病相关的病理性细胞和细胞因子特征指出了过度活化的先天免疫应答在驱动病理中的关键作用。COVID-19独特的免疫病理学特征包括骨髓细胞显性炎症和细胞因子释放综合征（CRS）以及淋巴细胞减少症和急性呼吸窘迫综合征（ARDS），所有这些都与严重疾病相关。研究表明，一系列的原因介导的骨髓超活化，如异常的先天感应，免疫细胞反应，以及直接的病毒蛋白/宿主相互作用。这些包括最近鉴定出的结合SARS-CoV-2的新的髓样细胞受体，其通过典型受体血管紧张素转换酶2（ACE 2）独立于肺上皮细胞感染驱动髓样细胞的炎症反应。COVID-19中骨髓细胞失调的范围和性质也至少在一定程度上不同于在其他涉及骨髓细胞活化的感染性疾病中观察到的情况。虽然大部分治疗工作都集中在疫苗或中和抗体阻断病毒感染的预防措施上，但最近的临床试验也针对骨髓细胞和相关细胞因子作为解决CRS和严重疾病的手段，具有有希望但迄今为止效果有限。在这篇综述中，我们批判性地研究了驱动骨髓细胞失调的潜在机制，导致免疫病理学和严重疾病，并讨论了靶向骨髓细胞的潜在治疗策略，作为COVID-19治疗的新范式。
The dysregulation of myeloid cell responses is increasingly demonstrated to be a major mechanism of pathogenesis for COVID-19. The pathological cellular and cytokine signatures associated with this disease point to a critical role of a hyperactivated innate immune response in driving pathology. Unique immunopathological features of COVID-19 include myeloid-cell dominant inflammation and cytokine release syndrome (CRS) alongside lymphopenia and acute respiratory distress syndrome (ARDS), all of which correlate with severe disease. Studies suggest a range of causes mediating myeloid hyperactivation, such as aberrant innate sensing, asynchronized immune cellular responses, as well as direct viral protein/host interactions. These include the recent identification of new myeloid cell receptors that bind SARS-CoV-2, which drive myeloid cell hyperinflammatory responses independently of lung epithelial cell infection via the canonical receptor, angiotensin-converting enzyme 2 (ACE2). The spectrum and nature of myeloid cell dysregulation in COVID-19 also differs from, at least to some extent, what is observed in other infectious diseases involving myeloid cell activation. While much of the therapeutic effort has focused on preventative measures with vaccines or neutralizing antibodies that block viral infection, recent clinical trials have also targeted myeloid cells and the associated cytokines as a means to resolve CRS and severe disease, with promising but thus far modest effects. In this review, we critically examine potential mechanisms driving myeloid cell dysregulation, leading to immunopathology and severe disease, and discuss potential therapeutic strategies targeting myeloid cells as a new paradigm for COVID-19 treatment.
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DOI：
10.1126/science.abd3072
发表时间：
2020-11-13
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Daly JL;Simonetti B;Klein K;Chen KE;Williamson MK;Antón-Plágaro C;Shoemark DK;Simón-Gracia L;Bauer M;Hollandi R;Greber UF;Horvath P;Sessions RB;Helenius A;Hiscox JA;Teesalu T;Matthews DA;Davidson AD;Collins BM;Cullen PJ;Yamauchi Y
通讯作者：
Yamauchi Y
影响因子：
120.7
作者：
Caricchio, Roberto;Abbate, Antonio;Noviello, Stephanie
通讯作者：
Noviello, Stephanie
影响因子：
5.2
作者：
Corrao S;Pinelli K;Vacca M;Raspanti M;Argano C
通讯作者：
Argano C
影响因子：
18.2
作者：
Cordova AF;Ritchie C;Böhnert V;Li L
通讯作者：
Li L
影响因子：
64.8
作者：
Delorey TM;Ziegler CGK;Heimberg G;Normand R;Yang Y;Segerstolpe Å;Abbondanza D;Fleming SJ;Subramanian A;Montoro DT;Jagadeesh KA;Dey KK;Sen P;Slyper M;Pita-Juárez YH;Phillips D;Biermann J;Bloom-Ackermann Z;Barkas N;Ganna A;Gomez J;Melms JC;Katsyv I;Normandin E;Naderi P;Popov YV;Raju SS;Niezen S;Tsai LT;Siddle KJ;Sud M;Tran VM;Vellarikkal SK;Wang Y;Amir-Zilberstein L;Atri DS;Beechem J;Brook OR;Chen J;Divakar P;Dorceus P;Engreitz JM;Essene A;Fitzgerald DM;Fropf R;Gazal S;Gould J;Grzyb J;Harvey T;Hecht J;Hether T;Jané-Valbuena J;Leney-Greene M;Ma H;McCabe C;McLoughlin DE;Miller EM;Muus C;Niemi M;Padera R;Pan L;Pant D;Pe'er C;Pfiffner-Borges J;Pinto CJ;Plaisted J;Reeves J;Ross M;Rudy M;Rueckert EH;Siciliano M;Sturm A;Todres E;Waghray A;Warren S;Zhang S;Zollinger DR;Cosimi L;Gupta RM;Hacohen N;Hibshoosh H;Hide W;Price AL;Rajagopal J;Tata PR;Riedel S;Szabo G;Tickle TL;Ellinor PT;Hung D;Sabeti PC;Novak R;Rogers R;Ingber DE;Jiang ZG;Juric D;Babadi M;Farhi SL;Izar B;Stone JR;Vlachos IS;Solomon IH;Ashenberg O;Porter CBM;Li B;Shalek AK;Villani AC;Rozenblatt-Rosen O;Regev A
通讯作者：
Regev A