title: Microbes and mucosal immune responses in asthma.
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.
authors: National Heart and Lung Institute, Centre for Respiratory Infection, MRC, London, UK. t.hansel@imperial.ac.uk
authors: Trevor T
authors: TT
authors: Hansel
authors: Sebastian L
authors: SL
authors: Johnston
authors: Peter J
authors: PJ
authors: Openshaw
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001249:Asthma / Q000276:immunology* / Q000382:microbiology*; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008875:Middle Aged; D020545:Respiratory Mucosa / Q000276:immunology* / Q000382:microbiology*; D055815:Young Adult