哮喘联盟

   摘要
   背景：人类鼻病毒（HRV）的感染被认为是哮喘恶化的主要诱因。哮喘患者抗病毒免疫反应异常，其气道结构细胞、骨髓来源迁移细胞均表现为免疫紊乱。虽然有报道称哮喘患者抗病毒干扰素（IFNs）的产生能力下降，但是其涉及的相关分子机制仍未被阐明。
   目的：比较哮喘患者及健康人来源的外周血单核细胞（PBMC）在人类鼻病毒刺激后I型干扰素合成能力的不同。
   方法：将从22例过敏性哮喘患者及20例健康人分离得到的外周血单核细胞与人类鼻病毒孵育24小时。在蛋白水平及mRNA水平比较两者间Toll样受体（TLR）的多种组分、干扰素合成相关调节蛋白以及NFκβ信号通路的不同。
   结果：哮喘患者对人类鼻病毒的固有免疫反应表现出多方面的缺陷，其IFNα、IFNβ及干扰素诱导基因的表达水平与正常人相比明显下降。同时，哮喘患者伴随细胞内信号传导分子的表达水平下降，其中包括干扰素调节因子（IRF1,IRF7）、NF-κB家族成员（p50, p52, p65和IκKα）以及STAT1，并且其对TLR7/TLR8激活的反应能力下降。这些变化不应归结于树突状细胞的数量异常或病毒RNA敏感受体（TLR7/TLR8）的基础表达量不同。在健康人群中，抑制I型IFN的活性或去除浆细胞样树突状细胞可使其表现出类似哮喘患者的异常。
   结论：哮喘患者固有抗病毒信号传导方面表现出多种异常，其IFN依赖及非IFN依赖的分子的表达均有异常。
 

（苏楠 审校）
PLoS One. 2014 Sep 9;9(9):e106501. doi: 10.1371/journal.pone.0106501. eCollection 2014.

 

Asthma is associated with multiple alterations in anti-viral innate signalling pathways.
 

Pritchard AL1, White OJ1, Burel JG1, Carroll ML1, Phipps S2, Upham JW3.
 

ABSTRACT
BACKGROUND:Human rhinovirus (HRV) infection is a major trigger for asthma exacerbations. Anti-viral immunity appears to be abnormal in asthma, with immune dysfunction reported in both airway structural cells and migratory, bone marrow derived cells. Though decreased capacity to produce anti-viral interferons (IFNs) has been reported in asthma, a detailed analysis of the molecular events involved has not been undertaken.
OBJECTIVE: To compare the molecular pathway controlling type I IFN synthesis in HRV-stimulated peripheral blood mononuclear cells (PBMC) from asthmatic and healthy subjects.
METHODS: PBMC from 22 allergic asthmatics and 20 healthy donors were cultured with HRV for 24 hours. Multiple components of the Toll-like receptor (TLR), IFN regulatory and NFκβ pathways were compared at the mRNA and protein level.
RESULTS: Multiple deficiencies in the innate immune response to HRV were identified in asthma, with significantly lower expression of IFNα, IFNβ and interferon stimulated genes than in healthy subjects. This was accompanied by reduced expression of intra-cellular signalling molecules including interferon regulatory factors (IRF1, IRF7), NF-κB family members (p50, p52, p65 and IκKα) and STAT1, and by reduced responsiveness to TLR7/TLR8 activation. These observations could not be attributed to alterations in the numbers of dendritic cell (DC) subsets in asthma or baseline expression of the viral RNA sensing receptors TLR7/TLR8. In healthy subjects, blocking the activity of type-I IFN or depleting plasmacytoid DC recapitulated many of the abnormalities observed in asthma.
CONCLUSIONS: Multiple abnormalities in innate anti-viral signalling pathways were identified in asthma, with deficiencies in both IFN-dependent and IFN-independent molecules identified.
 

PLoS One. 2014 Sep 9;9(9):e106501. doi: 10.1371/journal.pone.0106501. eCollection 2014.