TLR2 Activation Limits Rhinovirus-Stimulated CXCL-10 by Attenuating IRAK-1-Dependent IL-33 Receptor Signaling in Human Bronchial Epithelial Cells
| Autor: | Adam T. Comstock, Duc Thinh Pham, Uma S. Sajjan, Magdalena H. Hudy, Yaxun Jing, David Proud, Benjamin L. Unger, Mohammad Farazuddin, Shyamala Ganesan, Adam S. Lauring |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Chemokine Rhinovirus Immunology Interleukin-1 Receptor-Like 1 Protein Inflammation Bronchi Respiratory Mucosa Article Proinflammatory cytokine 03 medical and health sciences Mice medicine Immunology and Allergy Animals Humans Cells Cultured Innate immune system Picornaviridae Infections biology Epithelial Cells Interleukin-33 Immunity Innate Toll-Like Receptor 2 Cell biology Interleukin 33 Chemokine CXCL10 TLR2 030104 developmental biology Interleukin-1 Receptor-Associated Kinases biology.protein Cytokines medicine.symptom Signal transduction Chemokines Signal Transduction |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 197(6) |
| ISSN: | 1550-6606 |
| Popis: | Airway epithelial cells are the major target for rhinovirus (RV) infection and express proinflammatory chemokines and antiviral cytokines that play a role in innate immunity. Previously, we demonstrated that RV interaction with TLR2 causes ILR-associated kinase-1 (IRAK-1) depletion in both airway epithelial cells and macrophages. Further, IRAK-1 degradation caused by TLR2 activation was shown to inhibit ssRNA-induced IFN expression in dendritic cells. Therefore, in this study, we examined the role of TLR2 and IRAK-1 in RV-induced IFN-β, IFN-λ1, and CXCL-10, which require signaling by viral RNA. In airway epithelial cells, blocking TLR2 enhanced RV-induced expression of IFNs and CXCL-10. By contrast, IRAK-1 inhibition abrogated RV-induced expression of CXCL-10, but not IFNs in these cells. Neutralization of IL-33 or its receptor, ST2, which requires IRAK-1 for signaling, inhibited RV-stimulated CXCL-10 expression. In addition, RV induced expression of both ST2 and IL-33 in airway epithelial cells. In macrophages, however, RV-stimulated CXCL-10 expression was primarily dependent on TLR2/IL-1R. Interestingly, in a mouse model of RV infection, blocking ST2 not only attenuated RV-induced CXCL-10, but also lung inflammation. Finally, influenza- and respiratory syncytial virus–induced CXCL-10 was also found to be partially dependent on IL-33/ST2/IRAK-1 signaling in airway epithelial cells. Together, our results indicate that RV stimulates CXCL-10 expression via the IL-33/ST2 signaling axis, and that TLR2 signaling limits RV-induced CXCL-10 via IRAK-1 depletion at least in airway epithelial cells. To our knowledge, this is the first report to demonstrate the role of respiratory virus–induced IL-33 in the induction of CXCL-10 in airway epithelial cells. |
| Databáze: | OpenAIRE |
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