title: Th2-type cytokine-induced mucus metaplasia decreases susceptibility of human bronchial epithelium to rhinovirus infection.
abstract: Human rhinoviruses (RVs) are a major cause of exacerbations in asthma and other chronic airway diseases. A characteristic feature of asthmatic epithelium is goblet cell metaplasia and mucus hypersecretion. Bronchial epithelium is also an important source of lipid mediators, including pro- and antiinflammatory eicosanoids. By using air-liquid interface cultures of airway epithelium from patients with asthma and nonasthmatic control subjects, we compared RV16 replication-induced changes in mRNA expression of asthma candidate genes and eicosanoid production in the epithelium with or without IL-13-induced mucus metaplasia. Mucus metaplastic epithelium was characterized by a 20-fold less effective replication of RV16 and blunted changes in gene expression; this effect was seen to the same extent in patients with asthma and control subjects. We identified ciliary cells as the main target for RV16 by immunofluorescence imaging and demonstrated that the numbers of ciliary cells decreased in RV16-infected epithelium. RV16 infection of mucociliary epithelium resulted in overexpression of genes associated with bronchial remodeling (e.g., MUC5AC, FGF2, and HBEGF), induction of cyclooxygenase-2, and increased secretion of prostaglandins. These responses were similar in both studied groups. These data indicate that structural changes associated with mucus metaplasia renders airway epithelium less susceptible to RV infection. Thus, exacerbations of the lung disease caused by RV may result from severe impairment in mucociliary clearance or activation of immune defense rather than from preferential infection of mucus metaplastic epithelium. Repeated rhinoviral infections of compromised epithelium may contribute to the remodeling of the airways.
authors.affiliation: 1 Department of Medicine, Jagiellonian University Medical College, Krakow, Poland; and.
authors.forename: Bogdan
authors.initials: B
authors.lastname: Jakiela
authors.forename: Anna
authors.initials: A
authors.lastname: Gielicz
authors.forename: Hanna
authors.initials: H
authors.lastname: Plutecka
authors.forename: Magdalena
authors.initials: M
authors.lastname: Hubalewska-Mazgaj
authors.forename: Lucyna
authors.initials: L
authors.lastname: Mastalerz
authors.forename: Grazyna
authors.initials: G
authors.lastname: Bochenek
authors.forename: Jerzy
authors.initials: J
authors.lastname: Soja
authors.forename: Rafal
authors.initials: R
authors.lastname: Januszek
authors.forename: Alar
authors.initials: A
authors.lastname: Aab
authors.forename: Jacek
authors.initials: J
authors.lastname: Musial
authors.forename: Mübeccel
authors.initials: M
authors.lastname: Akdis
authors.forename: Cezmi A
authors.initials: CA
authors.lastname: Akdis
authors.forename: Marek
authors.initials: M
authors.lastname: Sanak
mesh_terms: D000328:Adult; D056151:Airway Remodeling; D001249:Asthma / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D001980:Bronchi / Q000276:immunology* / Q000473:pathology / Q000821:virology; D016022:Case-Control Studies; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D004198:Disease Susceptibility; D004847:Epithelial Cells / Q000276:immunology* / Q000473:pathology / Q000821:virology; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008297:Male; D008679:Metaplasia; D008875:Middle Aged; D009079:Mucociliary Clearance; D009093:Mucus / Q000378:metabolism*; D010850:Picornaviridae Infections / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D011453:Prostaglandins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012229:Rhinovirus / Q000254:growth & development / Q000276:immunology* / Q000472:pathogenicity; D018418:Th2 Cells / Q000276:immunology* / Q000821:virology; D013997:Time Factors; D014779:Virus Replication
chemical_list: D016207:Cytokines; C573420:ICAM1 protein, human; D011453:Prostaglandins; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1
keywords: airway epithelium; asthma; eicosanoids; mucus cell metaplasia; rhinoviral infections