Center of Allergy and Environment (ZAUM), Technical University of Munich and Helmholtz Center Munich, 80802, Munich, Germany.
Division of Physiological Chemistry 2, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
Mucosal Immunol. 2022 Mar;15(3):515-524. doi: 10.1038/s41385-021-00482-8. Epub 2022 Mar 15.
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.
单核细胞衍生的巨噬细胞（MDM）驱动严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）的炎症反应，并且是气道炎症中类二十烷酸的主要来源。在这里，我们报告称，来自 SARS-CoV-2 感染轻症患者的 MDM 表现出炎症转录和代谢印记，这种印记至少会持续 SARS-CoV-2 感染后 5 个月。来自 SARS-CoV-2 感染后康复患者的 MDM 显示出促解决因子下调和促炎类二十烷酸的产生增加，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的合成，并且在 SARS-CoV-2 感染后 3-5 个月仍然升高，但在感染后 12 个月已恢复到基线水平。用 SARS-CoV-2 刺突蛋白或 LPS 刺激会在新冠病毒后 MDM 中引发过度的前列腺素、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，从而驱动异常的巨噬细胞效应功能和类二十烷酸代谢，导致从轻度 COVID-19 中康复的患者出现长期免疫异常。
