Rhinovirus Induces Differential Expression of Th2-Promoting Epithelial Cytokines From Asthmatics Ex Vivo

Abstract

RationaleThe majority of childhood asthma exacerbations are provoked by rhinovirus (RV) infections, and these most often occur when allergies are also present. We propose this reflects the propensity of RV infection of epithelium to induce expression of Th2-promoting cytokines and that this occurs without altering the innate immune response of these cells to RV.MethodsEpithelial cells derived from sinonasal epithelium of asthmatics and non-asthmatics were cultured and infected with RV39. Cells and supernatants were collected at various time intervals. Quantitative PCR was used to measure gene expression for the Th2-inducing cytokines IL-25, IL-33, and TSLP, and innate immune cytokines IL-15, IFN-ß, and IL-18. Supernatants were assayed for cytokine protein secretion.ResultsmRNA levels for IL-25, IL-33, and TSLP were increased in asthmatics compared to non-asthmatics after infection with RV39 at 2 (IL-25), 4 (TSLP), and 24 hours (IL-33). mRNA levels were increased for IL-15, IFN-ß, and IL-18 though no differences were observed between asthmatics and non-asthmatics. Protein expression of IL-15 was comparably evident in both cohorts at 48 hours.ConclusionsIn contrast to non-asthmatics, RV-infected sinonasal epithelium derived from asthmatics express mRNA for cytokines important in the induction of Th2 immune deviation. Additionally, there was little difference in the expression of innate cytokines, specifically IL-15 and IL-18, which suggests that there is no defect in innate immune responses to RV amongst asthmatics. We propose instead that it is this RV-induced barrage of Th2-inducing cytokines that is responsible for asthma exacerbations. RationaleThe majority of childhood asthma exacerbations are provoked by rhinovirus (RV) infections, and these most often occur when allergies are also present. We propose this reflects the propensity of RV infection of epithelium to induce expression of Th2-promoting cytokines and that this occurs without altering the innate immune response of these cells to RV. The majority of childhood asthma exacerbations are provoked by rhinovirus (RV) infections, and these most often occur when allergies are also present. We propose this reflects the propensity of RV infection of epithelium to induce expression of Th2-promoting cytokines and that this occurs without altering the innate immune response of these cells to RV. MethodsEpithelial cells derived from sinonasal epithelium of asthmatics and non-asthmatics were cultured and infected with RV39. Cells and supernatants were collected at various time intervals. Quantitative PCR was used to measure gene expression for the Th2-inducing cytokines IL-25, IL-33, and TSLP, and innate immune cytokines IL-15, IFN-ß, and IL-18. Supernatants were assayed for cytokine protein secretion. Epithelial cells derived from sinonasal epithelium of asthmatics and non-asthmatics were cultured and infected with RV39. Cells and supernatants were collected at various time intervals. Quantitative PCR was used to measure gene expression for the Th2-inducing cytokines IL-25, IL-33, and TSLP, and innate immune cytokines IL-15, IFN-ß, and IL-18. Supernatants were assayed for cytokine protein secretion. ResultsmRNA levels for IL-25, IL-33, and TSLP were increased in asthmatics compared to non-asthmatics after infection with RV39 at 2 (IL-25), 4 (TSLP), and 24 hours (IL-33). mRNA levels were increased for IL-15, IFN-ß, and IL-18 though no differences were observed between asthmatics and non-asthmatics. Protein expression of IL-15 was comparably evident in both cohorts at 48 hours. mRNA levels for IL-25, IL-33, and TSLP were increased in asthmatics compared to non-asthmatics after infection with RV39 at 2 (IL-25), 4 (TSLP), and 24 hours (IL-33). mRNA levels were increased for IL-15, IFN-ß, and IL-18 though no differences were observed between asthmatics and non-asthmatics. Protein expression of IL-15 was comparably evident in both cohorts at 48 hours. ConclusionsIn contrast to non-asthmatics, RV-infected sinonasal epithelium derived from asthmatics express mRNA for cytokines important in the induction of Th2 immune deviation. Additionally, there was little difference in the expression of innate cytokines, specifically IL-15 and IL-18, which suggests that there is no defect in innate immune responses to RV amongst asthmatics. We propose instead that it is this RV-induced barrage of Th2-inducing cytokines that is responsible for asthma exacerbations. In contrast to non-asthmatics, RV-infected sinonasal epithelium derived from asthmatics express mRNA for cytokines important in the induction of Th2 immune deviation. Additionally, there was little difference in the expression of innate cytokines, specifically IL-15 and IL-18, which suggests that there is no defect in innate immune responses to RV amongst asthmatics. We propose instead that it is this RV-induced barrage of Th2-inducing cytokines that is responsible for asthma exacerbations.