Interleukin-13-induced mucous metaplasia increases susceptibility of human airway epithelium to rhinovirus infection.
Infection of airway epithelium by rhinovirus is the most common cause of asthma exacerbations. Even in mild asthma, airway epithelium exhibits mucous metaplasia, which increases with increasing severity of the disease. We previously showed that squamous cultures of human airway epithelium manifest rhinoviral infection at levels many times higher than in well-differentiated cultures of a mucociliary phenotype. Here we tested the hypothesis that mucous metaplasia is also associated with increased levels of rhinoviral infection. Mucous metaplasia was induced with IL-13, which doubled the numbers of goblet cells. In both control (mucociliary) and IL-13- treated (mucous metaplastic) cultures, goblet cells were preferentially infected by rhinovirus. IL-13 doubled the numbers of infected cells by increasing the numbers of infected goblet cells. Furthermore, IL-13 increased both the maturity of goblet cells and the probability that a goblet cell would be infected. The infection of cells other than goblet cells was unaltered by IL-13. Treatment with IL-13 did not alter the levels of rhinovirus receptor ICAM-1, nor did the proliferative effects of IL-13 enhance infection, because rhinovirus did not colocalize with dividing cells. However, the induction of mucous metaplasia caused changes in the apical membrane structure, notably a marked decrease in overall ciliation, and an increase in the overall flatness of the apical surface. We conclude that mucous metaplasia in asthma increases the susceptibility of airway epithelium to infection by rhinovirus because of changes in the overall architecture of the apical surface.
Lachowicz-Scroggins
Marrah E
ME
Department of Physiology and Membrane Biology, School of Medicine, University of California at Davis, One Shields Avenue, Davis, CA 95616-8643, USA. jhwiddicombe@ucdavis.edu
Boushey
Homer A
HA
Finkbeiner
Walter E
WE
Widdicombe
Jonathan H
JH
D002452:Cell Count; D002478:Cells, Cultured; D002923:Cilia / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D004198:Disease Susceptibility; D004847:Epithelial Cells / Q000276:immunology / Q000473:pathology / Q000648:ultrastructure / Q000821:virology; D004848:Epithelium / Q000187:drug effects / Q000473:pathology* / Q000821:virology*; D005455:Fluorescent Antibody Technique; D020397:Goblet Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology / Q000821:virology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D018793:Interleukin-13 / Q000494:pharmacology*; D019394:Ki-67 Antigen / Q000378:metabolism; D008679:Metaplasia / Q000139:chemically induced / Q000276:immunology; D009093:Mucus / Q000187:drug effects* / Q000276:immunology / Q000821:virology*; D010850:Picornaviridae Infections / Q000473:pathology / Q000821:virology*; D012229:Rhinovirus / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
D018793:Interleukin-13; D019394:Ki-67 Antigen; D018799:Intercellular Adhesion Molecule-1