哮喘中嗜酸性粒细胞捕获病毒的能力受损
2020/10/14
摘要
背景：活化的嗜酸粒细胞在哮喘稳定期和发作期中引起了主要的病理学改变。然而，它们也可以表现出保护性的特性，如细胞外抗病毒活性。最初的小鼠研究使我们进一步探索嗜酸性粒细胞潜在的细胞内抗病毒活性。
方法：荧光亲油性染料（DiD）标记的呼吸道合胞病毒（RSV）和流感病毒（流感病毒）用于观察嗜酸性粒细胞与病毒间的相互作用。共聚焦显微镜、电子显微镜和流式细胞术用于直观地观察病毒与嗜酸性粒细胞的相互作用。流式细胞术和ELISA用于检测嗜酸性粒细胞的活性。在一项单独的研究中，哮喘患者使用抗IL-5（美泊利单抗）使嗜酸性粒细胞减少，然后用鼻病毒-16（RV16）激发。
结果：DiD标记的RSV和流感病毒能迅速粘附在人嗜酸性粒细胞上，并被内化和灭活（95%在≤2小时内），而在上皮细胞中的反应减少。随着哮喘严重程度的加重，嗜酸性粒细胞捕获病毒的能力降低75%。嗜酸性粒细胞在体内外均被病毒激活。在体内，这与病毒引起的哮喘控制丧失有关。
结论：这一先前未被认识的、在哮喘中减弱的抗病毒特性为嗜酸性粒细胞在哮喘中的作用提供了一个新的视角。这表明嗜酸性粒细胞的保护性和细胞毒性之间存在不平衡，这可能是哮喘发作的基础。
Eosinophils capture viruses, a capacity that is defective in asthma.
Yanaika S Sabogal Piñeros, Suzanne M Bal, Annemiek Dijkhuis, Christof J Majoor, Barbara S Dierdorp, Tamara Dekker, Esmée P Hoefsmit, Peter I Bonta, Daisy Picavet, Nicole N van der Wel, Leo Koenderman, Peter J Sterk, Lara Ravanetti, René Lutter.
Abstract
BACKGROUND:Activated eosinophils cause major pathology in stable and exacerbating asthma; however, they can also display protective properties like an extracellular antiviral activity. Initial murine studies led us to further explore a potential intracellular antiviral activity by eosinophils.
METHODS:To follow eosinophil-virus interaction, respiratory syncytial virus (RSV) and influenza virus were labeled with a fluorescent lipophilic dye (DiD). Interactions with eosinophils were visualized by confocal microscopy, electron microscopy, and flow cytometry. Eosinophil activation was assessed by both flow cytometry and ELISA. In a separate study, eosinophils were depleted in asthma patients using anti-IL-5 (mepolizumab), followed by a challenge with rhinovirus-16 (RV16).
RESULTS:DiD-RSV and DiD-influenza rapidly adhered to human eosinophils and were internalized and inactivated (95% in ≤ 2 hours) as reflected by a reduced replication in epithelial cells. The capacity of eosinophils to capture virus was reduced up to 75% with increasing severity of asthma. Eosinophils were activated by virus in vitro and in vivo. In vivo this correlated with virus-induced loss of asthma control.
CONCLUSIONS:This previously unrecognized and in asthma attenuated antiviral property provides a new perspective to eosinophils in asthma. This is indicative of an imbalance between protective and cytotoxic properties by eosinophils that may underlie asthma exacerbations.
背景：活化的嗜酸粒细胞在哮喘稳定期和发作期中引起了主要的病理学改变。然而，它们也可以表现出保护性的特性，如细胞外抗病毒活性。最初的小鼠研究使我们进一步探索嗜酸性粒细胞潜在的细胞内抗病毒活性。
方法：荧光亲油性染料（DiD）标记的呼吸道合胞病毒（RSV）和流感病毒（流感病毒）用于观察嗜酸性粒细胞与病毒间的相互作用。共聚焦显微镜、电子显微镜和流式细胞术用于直观地观察病毒与嗜酸性粒细胞的相互作用。流式细胞术和ELISA用于检测嗜酸性粒细胞的活性。在一项单独的研究中，哮喘患者使用抗IL-5（美泊利单抗）使嗜酸性粒细胞减少，然后用鼻病毒-16（RV16）激发。
结果：DiD标记的RSV和流感病毒能迅速粘附在人嗜酸性粒细胞上，并被内化和灭活（95%在≤2小时内），而在上皮细胞中的反应减少。随着哮喘严重程度的加重，嗜酸性粒细胞捕获病毒的能力降低75%。嗜酸性粒细胞在体内外均被病毒激活。在体内，这与病毒引起的哮喘控制丧失有关。
结论：这一先前未被认识的、在哮喘中减弱的抗病毒特性为嗜酸性粒细胞在哮喘中的作用提供了一个新的视角。这表明嗜酸性粒细胞的保护性和细胞毒性之间存在不平衡，这可能是哮喘发作的基础。
(中日友好医院呼吸与危重症医学科 顾宪民 摘译 林江涛 审校)
(Allergy. 2019 Oct;74(10):1898-1909. doi: 10.1111/all.13802. Epub 2019 May 15.)
(Allergy. 2019 Oct;74(10):1898-1909. doi: 10.1111/all.13802. Epub 2019 May 15.)
Eosinophils capture viruses, a capacity that is defective in asthma.
Yanaika S Sabogal Piñeros, Suzanne M Bal, Annemiek Dijkhuis, Christof J Majoor, Barbara S Dierdorp, Tamara Dekker, Esmée P Hoefsmit, Peter I Bonta, Daisy Picavet, Nicole N van der Wel, Leo Koenderman, Peter J Sterk, Lara Ravanetti, René Lutter.
Abstract
BACKGROUND:Activated eosinophils cause major pathology in stable and exacerbating asthma; however, they can also display protective properties like an extracellular antiviral activity. Initial murine studies led us to further explore a potential intracellular antiviral activity by eosinophils.
METHODS:To follow eosinophil-virus interaction, respiratory syncytial virus (RSV) and influenza virus were labeled with a fluorescent lipophilic dye (DiD). Interactions with eosinophils were visualized by confocal microscopy, electron microscopy, and flow cytometry. Eosinophil activation was assessed by both flow cytometry and ELISA. In a separate study, eosinophils were depleted in asthma patients using anti-IL-5 (mepolizumab), followed by a challenge with rhinovirus-16 (RV16).
RESULTS:DiD-RSV and DiD-influenza rapidly adhered to human eosinophils and were internalized and inactivated (95% in ≤ 2 hours) as reflected by a reduced replication in epithelial cells. The capacity of eosinophils to capture virus was reduced up to 75% with increasing severity of asthma. Eosinophils were activated by virus in vitro and in vivo. In vivo this correlated with virus-induced loss of asthma control.
CONCLUSIONS:This previously unrecognized and in asthma attenuated antiviral property provides a new perspective to eosinophils in asthma. This is indicative of an imbalance between protective and cytotoxic properties by eosinophils that may underlie asthma exacerbations.
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