哮喘联盟

   摘要
   哮喘和特应性疾病的发病率快速增长，这可能与生活方式改变导致细菌暴露下降有关。近期的研究显示，主要的细菌微生物能维持基础免疫内稳定，能调节针对微生物的免疫反应。然而，一些呼吸道病毒感染可引起婴儿支气管炎和儿童喘息，导致哮喘发作。而过敏原能部分模拟感染物的作用。对宿主固有感受系统的深入研究以及近期开发的研究共生和致病微生物暴露的方法，有助于阐明微生物是怎样导致哮喘状态下的粘膜炎症的。呼吸道粘膜提供了关键的微生物界面，在此，上皮细胞和树突状细胞与一些功能各异的淋巴细胞相互作用。淋巴样细胞从而调控一些信号通路，包括固有的和特异性的信号通路，来调节宿主的粘膜免疫反应。固有免疫针对微生物产生反应的基础是病原相关分子模式和模式识别受体之间的相互作用，这与易感人群I型干扰素、促炎因子产生和Th2细胞信号通路活化相关。这些相互协调、动态的免疫反应导致哮喘的不同表现型，我们以哮喘的七个阶段进行了描述。了解微生物在特应性向哮喘转化中的作用以及导致哮喘发作的作用，为临床试验中评价新的治疗措施提供了证据。基于这些新的观点，特异性宿主生物标志物可能使个性化治疗在哮喘患者中变为现实。
 

（苏楠 审校）
Lancet.2013 Feb 18. pii: S0140-6736(12)62202-8. doi: 10.1016/S0140-6736(12)62202-8. [Epub ahead of print]

 

Microbes and mucosal immune responses in asthma.
 
Hansel TT, Johnston SL, Openshaw PJ.

Source
National Heart and Lung Institute (NHLI), Centre for Respiratory Infection (CRI), MRC and Asthma UK Centre for Allergic Mechanisms of Asthma, Imperial College, St Mary's Hospital, Norfolk Place, Paddington, London, UK. Electronic address: t.hansel@imperial.ac.uk.

Abstract
The substantial increase in the worldwide prevalence of asthma and atopy has been attributed to lifestyle changes that reduce exposure to bacteria. A recent insight is that the largely bacterial microbiome maintains a state of basal immune homoeostasis, which modulates immune responses to microbial pathogens. However, some respiratory viral infections cause bronchiolitis of infancy and childhood wheeze, and can exacerbate established asthma; whereas allergens can partly mimic infectious agents. New insights into the host's innate sensing systems, combined with recently developed methods that characterise commensal and pathogenic microbial exposure, now allow a unified theory for how microbes cause mucosal inflammation in asthma. The respiratory mucosa provides a key microbial interface where epithelial and dendritic cells interact with a range of functionally distinct lymphocytes. Lymphoid cells then control a range of pathways, both innate and specific, which organise the host mucosal immune response. Fundamental to innate immune responses to microbes are the interactions between pathogen-associated molecular patterns and pattern recognition receptors, which are associated with production of type I interferons, proinflammatory cytokines, and the T-helper-2 cell pathway in predisposed people. These coordinated, dynamic immune responses underlie the differing asthma phenotypes, which we delineate in terms of Seven Ages of Asthma. An understanding of the role of microbes in the atopic march towards asthma, and in causing exacerbations of established asthma, provides the rationale for new specific treatments that can be assessed in clinical trials. On the basis of these new ideas, specific host biomarkers might then allow personalised treatment to become a reality for patients with asthma.
 

Lancet.2013 Feb 18. pii: S0140-6736(12)62202-8. doi: 10.1016/S0140-6736(12)62202-8. [Epub ahead of print]