Dysregulated Neutrophil Phenotype and Function in Hospitalised Non-ICU COVID-19 Pneumonia.
Dysregulated Neutrophil Phenotype and Function in Hospitalised Non-ICU COVID-19 Pneumonia.
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DOI：
10.3390/cells11182901
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发表时间：
2022-09-16
期刊：
影响因子：
6
通讯作者：
Scott, Aaron
中科院分区：
文献类型：
--
作者：
Belchamber, Kylie B. R.;Thein, Onn S.;Hazeldine, Jon;Grudzinska, Frances S.;Faniyi, Aduragbemi A.;Hughes, Michael J.;Jasper, Alice E.;Yip, Kay Por;Crowley, Louise E.;Lugg, Sebastian T.;Sapey, Elizabeth;Parekh, Dhruv;Thickett, David R.;Scott, Aaron
原理：SARS-CoV 2病毒感染与中性粒细胞计数升高相关。COVID-19中中性粒细胞功能障碍的证据基于转录组学或单功能测定。细胞功能是相互交织的途径，了解中性粒细胞功能谱的影响可能会确定治疗靶点。目的：检查41名住院非ICU COVID-19患者与23名年龄匹配的对照（AMC）和26名社区获得性肺炎患者（CAP）的中性粒细胞表型和功能。方法：对分离的中性粒细胞进行迁移、细菌吞噬、ROS生成、NETosis和受体表达的离体分析。检测循环DNAse 1活性、cfDNA、MPO、VEGF、IL-6和sTNFRI水平，并与临床结局相关。还测量了住院后第三至第五天的连续采样。在另一组18名COVID-19患者中测量了离体PI 3 K抑制的效果。结果如下：与AMC和CAP相比，COVID-19中性粒细胞表现出迁移（p = 0.0397）和NETosis（p = 0.0332）升高，吞噬功能受损（p = 0.0036）与ROS生成受损（p < 0.0001）相关。在COVID-19中，CD 54+中性粒细胞的百分比（p < 0.001）显著增加，而CD 11b（p = 0.0014）和PD-L1（p = 0.006）的表面表达显著降低。COVID-19和CAP患者显示NETosis的全身标志物增加，包括cfDNA增加（p = 0.0396）和DNA酶活性受损（p < 0.0001）。PI 3 K γ和δ的离体抑制减少了COVID-19中性粒细胞的NET释放（p = 0.0129）。结论：COVID-19与所有主要效应子功能的中性粒细胞功能障碍相关，包括表型改变、迁移和NETosis增加以及抗菌反应受损。这些变化强调了靶向中性粒细胞功能可能有助于调节COVID-19的严重程度。
Rationale: Infection with the SARS-CoV2 virus is associated with elevated neutrophil counts. Evidence of neutrophil dysfunction in COVID-19 is based on transcriptomics or single functional assays. Cell functions are interwoven pathways, and understanding the effect across the spectrum of neutrophil function may identify therapeutic targets. Objectives: Examine neutrophil phenotype and function in 41 hospitalised, non-ICU COVID-19 patients versus 23 age-matched controls (AMC) and 26 community acquired pneumonia patients (CAP). Methods: Isolated neutrophils underwent ex vivo analyses for migration, bacterial phagocytosis, ROS generation, NETosis and receptor expression. Circulating DNAse 1 activity, levels of cfDNA, MPO, VEGF, IL-6 and sTNFRI were measured and correlated to clinical outcome. Serial sampling on day three to five post hospitalization were also measured. The effect of ex vivo PI3K inhibition was measured in a further cohort of 18 COVID-19 patients. Results: Compared to AMC and CAP, COVID-19 neutrophils demonstrated elevated transmigration (p = 0.0397) and NETosis (p = 0.0332), and impaired phagocytosis (p = 0.0036) associated with impaired ROS generation (p < 0.0001). The percentage of CD54+ neutrophils (p < 0.001) was significantly increased, while surface expression of CD11b (p = 0.0014) and PD-L1 (p = 0.006) were significantly decreased in COVID-19. COVID-19 and CAP patients showed increased systemic markers of NETosis including increased cfDNA (p = 0.0396) and impaired DNAse activity (p < 0.0001). The ex vivo inhibition of PI3K γ and δ reduced NET release by COVID-19 neutrophils (p = 0.0129). Conclusions: COVID-19 is associated with neutrophil dysfunction across all main effector functions, with altered phenotype, elevated migration and NETosis, and impaired antimicrobial responses. These changes highlight that targeting neutrophil function may help modulate COVID-19 severity.
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影响因子：
4.6
作者：
Arcanjo A;Logullo J;Menezes CCB;de Souza Carvalho Giangiarulo TC;Dos Reis MC;de Castro GMM;da Silva Fontes Y;Todeschini AR;Freire-de-Lima L;Decoté-Ricardo D;Ferreira-Pereira A;Freire-de-Lima CG;Barroso SPC;Takiya C;Conceição-Silva F;Savino W;Morrot A
通讯作者：
Morrot A
影响因子：
7.3
作者：
Hazeldine J;Lord JM
通讯作者：
Lord JM
影响因子：
5.3
作者：
通讯作者：
--
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)
影响因子：
21.3
作者：
Andrew, Natalie;Insall, Robert H.
通讯作者：
Insall, Robert H.