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Excessive inflammation during bacterial and viral infections is destructive to the host and involves elevated production of proinflammatory cytokines. It is especially deleterious in organs with space constraints such as lung and the CNS. Indeed, a number of viruses that infect lungs, such as avian influenza virus, SARS-associated coronavirus, and respiratory syncytial virus, elicit a very high level of proinflammatory cytokines; however, it is unclear what triggers their production. In this study, we show that IL-17 commonly produced during viral infection specifically augments a proinflammatory response by directly synergizing with antiviral signaling. Costimulation of primary human fibroblasts with IL-17 greatly enhanced respiratory syncytial virus-induced or synthetic dsRNA-based viral mimic polyinosinic:polycytidylic acid-induced expression of proinflammatory genes without affecting expression of IFN-β-stimulated or IFN-stimulated genes. Knockdown of expression of known mediators of the antiviral signaling pathway revealed that the IL-17-poly(I:C) synergy depends on the presence of the transcriptional factors RelA and IFN regulatory factor 3 and IκB kinases. Moreover, this synergy was blocked by an IκB kinase inhibitor, BAY 11-7082. These findings shed light on the molecular mechanisms behind IL-17-dependent immunopathology observed in viral infections.

Original publication




Journal article


J immunol

Publication Date





5357 - 5362


Antiviral Agents, Cells, Cultured, Cytokines, Fibroblasts, Gene Expression Regulation, Humans, I-kappa B Kinase, Inflammation Mediators, Interferon Regulatory Factor-3, Interleukin-17, Poly I-C, Respiratory Syncytial Viruses, Signal Transduction, Skin, Transcription Factor RelA, Up-Regulation