重症COVID-19患者中IFN-λ、IFN-γ及Toll样受体表达的变化
Alterations in the Expression of IFN Lambda, IFN Gamma and Toll-like Receptors in Severe COVID-19 Patients.
作者信息
Sorrentino Leonardo, Fracella Matteo, Frasca Federica, D'Auria Alessandra, Santinelli Letizia, Maddaloni Luca, Bugani Ginevra, Bitossi Camilla, Gentile Massimo, Ceccarelli Giancarlo, Turriziani Ombretta, Mastroianni Claudio Maria, Antonelli Guido, d'Ettorre Gabriella, Pierangeli Alessandra, Scagnolari Carolina
机构信息
Laboratory of Virology, Department of Molecular Medicine, Sapienza University of Rome, 00185 Rome, Italy.
Department of Public Health and Infectious Diseases, Sapienza University of Rome, Policlinico Umberto I of Rome, 00185 Rome, Italy.
出版信息
Microorganisms. 2023 Mar 8;11(3):689. doi: 10.3390/microorganisms11030689.
Contradictory results have been reported regarding interferon (IFN) lambda (λ1-3) and IFN gamma (γ) production in COVID-19 patients. To gain insight into the roles played by these IFNs in SARS-CoV-2 infection, IFNλ1-3 and IFNγ mRNA expression was evaluated in peripheral blood mononuclear cells (PBMCs) ( = 32) and in cells of paired bronchoalveolar lavages (BALs) ( = 12). Lower IFNλ1-3 values ( < 0.001 for IFNλ1 and 3 and = 0.013 for IFNλ2) in the PBMCs of severely ill patients were found compared to healthy donors ( = 15). Reduced levels of IFNγ were also detected in patients' PBMCs ( < 0.01) and BALs ( = 0.041) compared to healthy donors. The presence of secondary bacterial infections was associated with decreased IFNλ amounts in PBMCs ( = 0.001, = 0.015 and = 0.003, respectively) but increased concentrations of IFNλ3 ( = 0.022) in BALs. Patients with alterations in C-reactive protein, lactate dehydrogenase and D-dimer levels had decreased IFNλ1 and 3 ( = 0.003 and < 0.001) and increased IFNγ ( = 0.08) in PBMCs. Analyzing Toll-like receptors (TLRs) involved in IFN production, we found that TLR3 was highly expressed ( = 0.033) in patients with bacterial superinfections, while TLR7 and 8 ( = 0.029 and = 0.049) were reduced in BALs of deceased patients. Overall, severe COVID-19 might be characterized by dysregulation in IFNγ, IFNλ and TLR3, 7 and 8 production.
关于新冠病毒疾病（COVID-19）患者体内干扰素（IFN）λ（λ1 - 3）和干扰素γ（γ）的产生，已有相互矛盾的报道。为深入了解这些干扰素在严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染中所起的作用，我们评估了32例患者外周血单个核细胞（PBMCs）以及12例配对支气管肺泡灌洗（BAL）细胞中IFNλ1 - 3和IFNγ的mRNA表达。与15名健康供体相比，重症患者PBMCs中的IFNλ1 - 3值较低（IFNλ1和3 < 0.001，IFNλ2 = 0.013）。与健康供体相比，患者PBMCs（< 0.01）和BAL（ = 0.041）中的IFNγ水平也有所降低。继发性细菌感染的存在与PBMCs中IFNλ量的减少相关（分别为 = 0.001、 = 0.015和 = 0.003），但BAL中IFNλ3的浓度增加（ = 0.022）。C反应蛋白、乳酸脱氢酶和D - 二聚体水平发生改变的患者，其PBMCs中IFNλ1和3降低（ = 0.003和 < 0.001），IFNγ增加（ = 0.08）。分析参与干扰素产生的Toll样受体（TLR），我们发现细菌重叠感染患者中TLR3高表达（ = 0.033），而死亡患者BAL中的TLR7和8降低（ = 0.029和 = 0.049）。总体而言，重症COVID - 19可能的特征是IFNγ、IFNλ以及TLR3、7和8产生的失调。
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