Rhinovirus-Induced Modulation of Epithelial Phenotype: Role in Asthma

Abstract

Human rhinoviruses have been linked both to the susceptibility of asthma development and to the triggering of acute exacerbations. Given that the human airway epithelial cell is the primary site of human rhinovirus (HRV) infection and replication, the current review focuses on how HRV-induced modulation of several aspects of epithelial cell phenotype could contribute to the development of asthma or to the induction of exacerbations. Modification of epithelial proinflammatory and antiviral responses are considered, as are alterations in an epithelial barrier function and cell phenotype. The contributions of the epithelium to airway remodeling and to the potential modulation of immune responses are also considered. The potential interactions of each type of HRV-induced epithelial phenotypic changes with allergic sensitization and allergic phenotype are also considered in the context of asthma development and of acute exacerbations.

Keywords: airway remodeling; asthma; barrier function; chemokines; epithelial cell; metabolism; rhinovirus.

Figure 1

Human rhinovirus (HRV) infection of human airway epithelial cells can generate multiple chemokines that can recruit and/or activate numerous inflammatory cell populations.

Figure 2

Human rhinovirus (HRV) infection and allergic stimulation can both induce epithelial production of IL-33, IL-25, and thymic stromal lymphopoietin (TSLP) that will stimulate activation of ILC2 cells to drive Th2 inflammation.