SARS-CoV-2 Dysregulates Neutrophil Degranulation and Reduces Lymphocyte Counts.
SARS-CoV-2 Dysregulates Neutrophil Degranulation and Reduces Lymphocyte Counts.
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DOI：
10.3390/biomedicines10020382
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发表时间：
2022-02-04
期刊：
影响因子：
4.7
通讯作者：
Reid SP
中科院分区：
文献类型：
--
作者：
Muralidharan A;Wyatt TA;Reid SP
SARS-CoV-2 是导致 COVID-19 的病毒，已引发最大的流行病之一，影响了全球数百万人。中性粒细胞与淋巴细胞比率高已被确定为重症 COVID-19 患者康复率差的重要相关因素。然而，这种临床结果的机制及其与不良预后相关的原因尚不清楚。此外，健康中性粒细胞获得 SARS-CoV-2 介导的有害作用的机制尚未完全了解。在这项研究中，我们从健康供体中分离出循环中性粒细胞，用受感染上皮细胞的上清液进行处理，并在体外直接感染 SARS-CoV-2。受感染的上皮细胞诱导初级颗粒脱颗粒失调，髓过氧化物酶（MPO）减少，但中性粒细胞弹性蛋白酶释放略有增加。尽管 CD16 受体脱落上调，中性粒细胞感染仍导致 MPO 和弹性蛋白酶释放受损。重要的是，感染 SARS-CoV-2 的中性粒细胞对外周血淋巴细胞计数有直接影响，CD19+ B 细胞、CD8+ T 细胞和 CD4+ T 细胞数量减少。总之，这项研究强调了中性粒细胞在 SARS-CoV-2 感染期间观察到的异常免疫反应中的独立作用，这些免疫反应在其他免疫细胞存在的情况下可能会进一步失调。
SARS-CoV-2, the virus that causes COVID-19, has given rise to one of the largest pandemics, affecting millions worldwide. High neutrophil-to-lymphocyte ratios have been identified as an important correlate to poor recovery rates in severe COVID-19 patients. However, the mechanisms underlying this clinical outcome and the reasons for its correlation to poor prognosis are unclear. Furthermore, the mechanisms involved in healthy neutrophils acquiring a SARS-CoV-2-mediated detrimental role are yet to be fully understood. In this study, we isolated circulating neutrophils from healthy donors for treatment with supernates from infected epithelial cells and direct infection with SARS-CoV-2 in vitro. Infected epithelial cells induced a dysregulated degranulation of primary granules with a decrease in myeloperoxidase (MPO), but slight increase in neutrophil elastase release. Infection of neutrophils resulted in an impairment of both MPO and elastase release, even though CD16 receptor shedding was upregulated. Importantly, SARS-CoV-2-infected neutrophils had a direct effect on peripheral blood lymphocyte counts, with decreasing numbers of CD19+ B cells, CD8+ T cells, and CD4+ T cells. Together, this study highlights the independent role of neutrophils in contributing to the aberrant immune responses observed during SARS-CoV-2 infection that may be further dysregulated in the presence of other immune cells.
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影响因子：
12.3
作者：
Aschenbrenner AC;Mouktaroudi M;Krämer B;Oestreich M;Antonakos N;Nuesch-Germano M;Gkizeli K;Bonaguro L;Reusch N;Baßler K;Saridaki M;Knoll R;Pecht T;Kapellos TS;Doulou S;Kröger C;Herbert M;Holsten L;Horne A;Gemünd ID;Rovina N;Agrawal S;Dahm K;van Uelft M;Drews A;Lenkeit L;Bruse N;Gerretsen J;Gierlich J;Becker M;Händler K;Kraut M;Theis H;Mengiste S;De Domenico E;Schulte-Schrepping J;Seep L;Raabe J;Hoffmeister C;ToVinh M;Keitel V;Rieke G;Talevi V;Skowasch D;Aziz NA;Pickkers P;van de Veerdonk FL;Netea MG;Schultze JL;Kox M;Breteler MMB;Nattermann J;Koutsoukou A;Giamarellos-Bourboulis EJ;Ulas T;German COVID-19 Omics Initiative (DeCOI)
通讯作者：
German COVID-19 Omics Initiative (DeCOI)
DOI：
10.1164/rccm.202002-0445oc
发表时间：
2020-06-01
影响因子：
24.7
作者：
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30.3
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通讯作者：
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