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) beta1 and IFN-lambda1 was assessed by quantitative reverse-transcriptase polymerase chain reaction and the protein level of IFN- lambda1 by enzyme-linked immunosorbent assay. RESULTS: Both poly(I:C) and HRV1A infection induced BEAS-2B expression of IFN-beta1 and IFN-lambda1 mRNA. Coculture of eosinophils resulted in suppression of poly(I:C)-stimulated IFN-beta1 and IFN-lambda1 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-beta1 and IFN-lambda1 mRNA (5.7-fold and 5.0-fold less, respectively) and reduced IFN-lambda1 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-lambda1 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.