Title | Rhinovirus inhibits IL-17A and the downstream immune responses in allergic asthma. | ||
Author | Graser, A; Ekici, A B; Sopel, N; Melichar, V O; Zimmermann, T; Papadopoulos, N G; Taka, S; Ferrazzi, F; Vuorinen, T; Finotto, S | ||
Journal | Mucosal Immunol | Publication Year/Month | 2016-Sep |
PMID | 26732679 | PMCID | PMC7099698 |
Affiliation + expend | 1.Department of Molecular Pneumology, Universitatsklinikum Erlangen, Erlangen, Germany. |
The proinflammatory cytokine interleukin-17A (IL-17A) is known to mediate antimicrobial activity, but its role during rhinovirus (RV) infections and in asthma needs further investigation. Therefore, we addressed the role of IL-17A during allergic asthma and antiviral immune response in human and murine immunocompetent cells. In this study we found that asthmatic children with a RV infection in their upper airways have upregulated mRNA levels of the antiviral cytokine interferon type I (IFN)-beta and the transcription factor T-box 21 (TBX21) and reduced levels of IL-17A protein in their peripheral blood mononuclear cells (PBMCs). We also found that IL-17A inhibited RV1b replication in infected human lung epithelial cells A549. Furthermore, by using gene array analysis we discovered that targeted deletion of Il17a in murine lung CD4(+) T cells impaired Oas1g mRNA downstream of Ifnbeta, independently from RV infection. Additionally, in PBMCs of children with a RV infection in their nasalpharyngeal fluid OAS1 gene expression was found downregulated. Finally RV1b inhibited IL-17A production in lung CD4(+) T cells in a setting of experimental asthma. These results indicate that the RV1b inhibits IL-17A in T helper type 17 cells and IL-17A clears RV1b infection in epithelial cells. In both cases IL-17A contributes to fend off RV1b infection by inducing genes downstream of interferon type I pathway.