Interaction between allergy and innate immunity: model for eosinophil regulation of epithelial cell interferon expression

Background: Eosinophils in asthmatic airways are associated with risk of exacerbations. The most common cause of asthma exacerbations is viral respiratory infections, particularly human rhinovirus (HRV). Objective: To determine the mechanism by which eosinophils may influence virus-induced responses. Methods: We used an in vitro coculture model of primary human eosinophils and the BEAS-2B epithelial cell line either stimulated with HRV1A infection or polyinosinic-polycytidylic acid (poly[I: C]). The messenger RNA (mRNA) expression of interferon (IFN) beta 1 and IFN-lambda 1 was assessed by quantitative reverse-transcriptase polymerase chain reaction and the protein level of IFN-lambda 1 by enzyme-linked immunosorbent assay. Results: Both poly(I: C) and HRV1A infection induced BEAS-2B expression of IFN-beta 1 and IFN-lambda 1 mRNA. Coculture of eosinophils resulted in suppression of poly(I: C)-stimulated IFN-beta 1 and IFN-lambda 1 mRNA expression (2.5-fold and 3.6-fold less, respectively). Separation of cells did not block eosinophil regulatory activity. Coculture of eosinophils with HRV1A-infected BEAS-2B cells also suppressed IFN-beta 1 and IFN-lambda 1 mRNA (5.7fold and 5.0-fold less, respectively) and reduced IFN-lambda 1 protein secretion (1.6-fold decrease). This corresponded to a 34% increase in the quantity of HRV1A virus RNA on coculture with eosinophils. Recombinant transforming growth factor beta suppressed IFN-lambda 1 from HRV1A-infected BEAS-2B cells. Coculture of eosinophils and BEAS-2B cells induced transforming growth factor beta secretion, which may mediate suppression of HRV-induced interferon expression. Conclusion: Eosinophils suppressed HRV-induced expression of interferons from epithelial cells, resulting in increased quantity of HRV. This represents one mechanism for interaction between allergic inflammation and innate immunity. (C) 2013 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.