Douville Renée N, Bastien Nathalie, Li Yan, Simons F Estelle R, HayGlass Kent T
CIHR National Training Program in Allergy and Asthma Research, Department of Immunology, University of Manitoba, 603 Basic Medical Sciences Building, 730 William Ave, Winnipeg, MB R3E0W3, Canada.
Biochem Cell Biol. 2007 Apr;85(2):252-8. doi: 10.1139/O07-005.
Human metapneumovirus and respiratory syncytial virus are RNA viruses associated with lower respiratory tract infections. Regular symptomatic re-infection and sequelae are common, particularly in individuals with pre-existing respiratory diseases, such as asthma. Our understanding of virus-dependent cytokine responses and potential differences between allergic asthmatics and non-asthmatics is limited. To test our hypothesis that adults with mild allergic asthma, the most common form of this disease, exhibit distinct pro-inflammatory responses, we developed a model using acute in vitro infection of fresh peripheral blood mononuclear cells. For both viruses, the production of innate-immunity-associated IL-6 and IL-10 was indistinguishable in the 2 populations. Type 1 cytokine production dominated adaptive immune responses in both asthmatic and non-asthmatic individuals. Surprisingly, asthmatics exhibited stronger pro-inflammatory IFNgamma production in response to human metapneumovirus than non-asthmatic adults (p = 0.01), with a similar, but statistically nonsignificant trend in the respiratory-syncytial-virus-stimulated response. Neutralizing IL-10 did not enhance the intensity of IFNgamma responses, demonstrating that this pro-inflammatory bias is not counter-regulated by IL-10. Finally, anti-TLR4 blocked lipopolysaccharide, but not respiratory-syncytial-virus-driven cytokine production. Collectively, the data demonstrate that asthma is characterized by markedly stronger pro-inflammatory IFNgamma responses to pneumoviruses than their non-asthmatic counterparts. This distinctive pattern of viral immunity may contribute to a worsening of asthma symptoms during respiratory virus infections.
人偏肺病毒和呼吸道合胞病毒是与下呼吸道感染相关的RNA病毒。反复出现症状性再感染和后遗症很常见，尤其是在患有如哮喘等原有呼吸道疾病的个体中。我们对病毒依赖性细胞因子反应以及过敏性哮喘患者与非哮喘患者之间潜在差异的了解有限。为了验证我们的假设，即患有轻度过敏性哮喘（该疾病最常见的形式）的成年人表现出不同的促炎反应，我们建立了一个使用新鲜外周血单个核细胞进行急性体外感染的模型。对于这两种病毒，在这两类人群中，与先天免疫相关的白细胞介素-6和白细胞介素-10的产生没有差异。1型细胞因子的产生在哮喘患者和非哮喘患者的适应性免疫反应中均占主导。令人惊讶的是，与非哮喘成年人相比，哮喘患者在感染人偏肺病毒后表现出更强的促炎干扰素γ产生（p = 0.01），在呼吸道合胞病毒刺激的反应中也有类似但无统计学意义的趋势。中和白细胞介素-10并没有增强干扰素γ反应的强度，表明这种促炎倾向不受白细胞介素-10的反向调节。最后，抗Toll样受体4阻断了脂多糖，但未阻断呼吸道合胞病毒驱动的细胞因子产生。总体而言，数据表明哮喘的特征是对肺病毒的促炎干扰素γ反应明显强于非哮喘患者。这种独特的病毒免疫模式可能导致呼吸道病毒感染期间哮喘症状恶化。
