Mild COVID-19 imprints a long-term inflammatory eicosanoid- and chemokine memory in monocyte-derived macrophages.
Mild COVID-19 imprints a long-term inflammatory eicosanoid- and chemokine memory in monocyte-derived macrophages.
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DOI：
10.1038/s41385-021-00482-8
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发表时间：
2022-03
影响因子：
8
通讯作者：
Esser-von Bieren, Julia
中科院分区：
文献类型：
--
作者：
Bohnacker, Sina;Hartung, Franziska;Henkel, Fiona;Quaranta, Alessandro;Kolmert, Johan;Priller, Alina;Ud-Dean, Minhaz;Giglberger, Johanna;Kugler, Luisa M.;Pechtold, Lisa;Yazici, Sarah;Lechner, Antonie;Erber, Johanna;Protzer, Ulrike;Lingor, Paul;Knolle, Percy;Chaker, Adam M.;Schmidt-Weber, Carsten B.;Wheelock, Craig E.;Esser-von Bieren, Julia
单核细胞衍生的巨噬细胞（MDM）驱动对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的炎症反应，并且它们是气道炎症中类花生酸的主要来源。在这里，我们报告说，MDM从SARS-CoV-2感染的个人与轻度疾病显示炎性转录和代谢印记，持续至少5个月后，SARS-CoV-2感染。来自恢复期SARS-CoV-2感染个体的MDM表现出促消退因子的下调和促炎性类花生酸的产生增加，特别是5-脂氧合酶衍生的白三烯。糖皮质激素进一步增强了白三烯合成，并在3-5个月时保持升高，但在SARS-CoV-2感染后12个月时恢复到基线水平。SARS-CoV-2刺突蛋白或LPS刺激在COVID-19后MDM中引发了过度的前列腺素类、I型IFN-和趋化因子反应。因此，SARS-CoV-2感染在单核细胞/巨噬细胞区室中留下炎症印记，驱动异常的巨噬细胞效应子功能和类花生酸代谢，导致从轻度COVID-19中恢复的患者的长期免疫畸变。
Monocyte-derived macrophages (MDM) drive the inflammatory response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and they are a major source of eicosanoids in airway inflammation. Here we report that MDM from SARS-CoV-2-infected individuals with mild disease show an inflammatory transcriptional and metabolic imprint that lasts for at least 5 months after SARS-CoV-2 infection. MDM from convalescent SARS-CoV-2-infected individuals showed a downregulation of pro-resolving factors and an increased production of pro-inflammatory eicosanoids, particularly 5-lipoxygenase-derived leukotrienes. Leukotriene synthesis was further enhanced by glucocorticoids and remained elevated at 3–5 months, but had returned to baseline at 12 months post SARS-CoV-2 infection. Stimulation with SARS-CoV-2 spike protein or LPS triggered exaggerated prostanoid-, type I IFN-, and chemokine responses in post COVID-19 MDM. Thus, SARS-CoV-2 infection leaves an inflammatory imprint in the monocyte/ macrophage compartment that drives aberrant macrophage effector functions and eicosanoid metabolism, resulting in long-term immune aberrations in patients recovering from mild COVID-19.
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DOI：
10.1073/pnas.2017527118
发表时间：
2021-03-02
影响因子：
11.1
作者：
Körner A;Bernard A;Fitzgerald JC;Alarcon-Barrera JC;Kostidis S;Kaussen T;Giera M;Mirakaj V
通讯作者：
Mirakaj V
影响因子：
4.4
作者：
Coffey, MJ;Phare, SM;Peters-Golden, M
通讯作者：
Peters-Golden, M
影响因子：
7.4
作者：
Kolmert, Johan;Fauland, Alexander;Wheelock, Craig E.
通讯作者：
Wheelock, Craig E.
影响因子：
8
作者：
Jaiswal AK;Yadav J;Makhija S;Mazumder S;Mitra AK;Suryawanshi A;Sandey M;Mishra A
通讯作者：
Mishra A
影响因子：
30.5
作者：
Aegerter, Helena;Kulikauskaite, Justina;Wack, Andreas
通讯作者：
Wack, Andreas