重症哮喘自然杀伤细胞的异常抗病毒反应
2020/06/11
摘要
鼻病毒感染是哮喘加重的主要原因。自然杀伤(NK)细胞是抗病毒先天应答的重要参与者，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。用类病原体分子或鼻病毒(RV)-A9和RV-2刺激重症哮喘患者和健康供者的外周血单核细胞，分析NK细胞的活化,脱颗粒和干扰素(IFN) -γ的表达。在toll样受体(TLR)3、TLR7/8或RV-A9作用下，重症哮喘患者NK细胞的细胞毒性小于健康供者，但在RV-2刺激下则无明显变化。此外,当与病毒感染期间产生的细胞因子白介素(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,表达的IFN-γ也低于健康捐赠者的NK细胞。重症哮喘NK细胞表现出耗竭表型，检查点分子Tim-3表达增加。综上所述，我们的研究结果表明，在某些但不是所有的呼吸道感染中，重症哮喘患者NK细胞的激活可能不足。耗竭表型可能参与了这些患者NK细胞损伤和病毒诱发哮喘加重。
Aberrant Anti-Viral Response of Natural Killer Cells in Severe Asthma
Justine Devulder , Cécile Chenivesse , Valérie Ledroit, Stéphanie Fry , Pierre-Emmanuel Lobert , Didier Hober, Anne Tsicopoulos , Catherine Duez
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 interferon (IFN)-γ expression were analysed. NK cells from severe asthma patients were less cytotoxic than those from healthy donors in response to toll-like receptor (TLR)3, TLR7/8 or RV-A9 but not in response to RV-2 stimulation. Furthermore, when cultured with interleukin (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。自然杀伤(NK)细胞是抗病毒先天应答的重要参与者，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。用类病原体分子或鼻病毒(RV)-A9和RV-2刺激重症哮喘患者和健康供者的外周血单核细胞，分析NK细胞的活化,脱颗粒和干扰素(IFN) -γ的表达。在toll样受体(TLR)3、TLR7/8或RV-A9作用下，重症哮喘患者NK细胞的细胞毒性小于健康供者，但在RV-2刺激下则无明显变化。此外,当与病毒感染期间产生的细胞因子白介素(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,表达的IFN-γ也低于健康捐赠者的NK细胞。重症哮喘NK细胞表现出耗竭表型，检查点分子Tim-3表达增加。综上所述，我们的研究结果表明，在某些但不是所有的呼吸道感染中，重症哮喘患者NK细胞的激活可能不足。耗竭表型可能参与了这些患者NK细胞损伤和病毒诱发哮喘加重。
(中日友好医院呼吸与危重症医学科 张清 摘译 林江涛 审校 )
(Eur Respir J. 2020 May 14;55(5):1802422.doi: 10.1183/13993003.02422-2018. Eur Respir J. 2020 May 14;55(5):1802422.doi: 10.1183/13993003.02422-2018.)
(Eur Respir J. 2020 May 14;55(5):1802422.doi: 10.1183/13993003.02422-2018. Eur Respir J. 2020 May 14;55(5):1802422.doi: 10.1183/13993003.02422-2018.)
Aberrant Anti-Viral Response of Natural Killer Cells in Severe Asthma
Justine Devulder , Cécile Chenivesse , Valérie Ledroit, Stéphanie Fry , Pierre-Emmanuel Lobert , Didier Hober, Anne Tsicopoulos , Catherine Duez
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 interferon (IFN)-γ expression were analysed. NK cells from severe asthma patients were less cytotoxic than those from healthy donors in response to toll-like receptor (TLR)3, TLR7/8 or RV-A9 but not in response to RV-2 stimulation. Furthermore, when cultured with interleukin (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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