重症哮喘中自然杀伤细胞的异常抗病毒反应
2020/03/11
摘要
鼻病毒感染是哮喘加重的主要原因。由于自然杀伤细胞（NK）是抗病毒天然应答的重要组成，我们旨在评估重症哮喘患者NK细胞对鼻病毒样分子或鼻病毒的应答功能。重症哮喘患者和健康对照外周血单个核细胞应用病原体样分子或鼻病毒（RV-A9和RV-2）刺激。分析NK细胞活化、脱颗粒及IFN-γ的表达。重症哮喘患者的NK细胞对TLR3、TLR7/8或RV-A9的杀伤作用低于健康人，对RV-2无差异。此外，与病毒感染过程中产生的细胞因子IL-12+IL-15一起培养时，重症哮喘患者NK细胞的细胞毒性较低，IFN-γ的表达也较正常人少。重症哮喘患者的NK细胞表现出衰竭的表型，Tim-3的表达增加。综上所述，我们的研究结果表明，重症哮喘患者的NK细胞在某些但并非所有的呼吸道感染中可能活化不足。衰竭表型可能参与NK细胞损伤和病毒性哮喘加重。
Aberrant anti-viral response of Natural Killer cell in severe asthma.
Devulder J, Chenivesse C, Ledroit V, Fry S, Lobert PE, Hober D, Tsicopoulos A, Duez C.
Abstract
Rhinovirus infections are the main cause of asthma exacerbations. As Natural Killer (NK) cells are important actors of the antiviral innate response, we aimed at evaluating the functions of NK cells from severe asthma patients in response to rhinovirus-like molecules or rhinoviruses. Peripheral blood mononuclear cells from patients with severe asthma and healthy donors were stimulated with pathogen-like molecules or with the rhinoviruses (RV)-A9 and RV-2. NK cell activation, degranulation and IFN-γ expression were analysed. NK cells from severe asthma patients were less cytotoxic than those from healthy donors in response to TLR3, TLR7/8 or RV-A9 but not in response to RV-2 stimulation. Furthermore, when cultured with IL-12+IL-15, cytokines which are produced during viral infections, NK cells from patients with severe asthma were less cytotoxic and expressed less IFN-γ than NK cells from healthy donors. NK cells from severe asthmatics exhibited an exhausted phenotype, with an increased expression of the checkpoint molecule Tim-3. Together, our findings indicate that the activation of NK cells from patients with severe asthma may be insufficient during some but not all respiratory infections. The exhausted phenotype may participate in NK cell impairment and aggravation of viral-induced asthma exacerbation in these patients.
鼻病毒感染是哮喘加重的主要原因。由于自然杀伤细胞（NK）是抗病毒天然应答的重要组成，我们旨在评估重症哮喘患者NK细胞对鼻病毒样分子或鼻病毒的应答功能。重症哮喘患者和健康对照外周血单个核细胞应用病原体样分子或鼻病毒（RV-A9和RV-2）刺激。分析NK细胞活化、脱颗粒及IFN-γ的表达。重症哮喘患者的NK细胞对TLR3、TLR7/8或RV-A9的杀伤作用低于健康人，对RV-2无差异。此外，与病毒感染过程中产生的细胞因子IL-12+IL-15一起培养时，重症哮喘患者NK细胞的细胞毒性较低，IFN-γ的表达也较正常人少。重症哮喘患者的NK细胞表现出衰竭的表型，Tim-3的表达增加。综上所述，我们的研究结果表明，重症哮喘患者的NK细胞在某些但并非所有的呼吸道感染中可能活化不足。衰竭表型可能参与NK细胞损伤和病毒性哮喘加重。
(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)
(Eur Respir J. 2020 Feb 27. pii: 1802422. doi: 10.1183/13993003.02422-2018.)
(Eur Respir J. 2020 Feb 27. pii: 1802422. doi: 10.1183/13993003.02422-2018.)
Aberrant anti-viral response of Natural Killer cell in severe asthma.
Devulder J, Chenivesse C, Ledroit V, Fry S, Lobert PE, Hober D, Tsicopoulos A, Duez C.
Abstract
Rhinovirus infections are the main cause of asthma exacerbations. As Natural Killer (NK) cells are important actors of the antiviral innate response, we aimed at evaluating the functions of NK cells from severe asthma patients in response to rhinovirus-like molecules or rhinoviruses. Peripheral blood mononuclear cells from patients with severe asthma and healthy donors were stimulated with pathogen-like molecules or with the rhinoviruses (RV)-A9 and RV-2. NK cell activation, degranulation and IFN-γ expression were analysed. NK cells from severe asthma patients were less cytotoxic than those from healthy donors in response to TLR3, TLR7/8 or RV-A9 but not in response to RV-2 stimulation. Furthermore, when cultured with IL-12+IL-15, cytokines which are produced during viral infections, NK cells from patients with severe asthma were less cytotoxic and expressed less IFN-γ than NK cells from healthy donors. NK cells from severe asthmatics exhibited an exhausted phenotype, with an increased expression of the checkpoint molecule Tim-3. Together, our findings indicate that the activation of NK cells from patients with severe asthma may be insufficient during some but not all respiratory infections. The exhausted phenotype may participate in NK cell impairment and aggravation of viral-induced asthma exacerbation in these patients.
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