| First Author | Guabiraba R | Year | 2013 |
| Journal | Eur J Immunol | Volume | 43 |
| Issue | 6 | Pages | 1529-44 |
| PubMed ID | 23505056 | Mgi Jnum | J:198121 |
| Mgi Id | MGI:5495565 | Doi | 10.1002/eji.201243229 |
| Citation | Guabiraba R, et al. (2013) IL-22 modulates IL-17A production and controls inflammation and tissue damage in experimental dengue infection. Eur J Immunol 43(6):1529-44 |
| abstractText | Dengue virus (DENV), a mosquito-borne flavivirus, is a public health problem in many tropical countries. IL-22 and IL-17A are key cytokines in several infectious and inflammatory diseases. We have assessed the contribution of IL-22 and IL-17A in the pathogenesis of experimental dengue infection using a mouse-adapted DENV serotype 2 strain (P23085) that causes a disease that resembles severe dengue in humans. We show that IL-22 and IL-17A are produced upon DENV-2 infection in immune-competent mice. Infected IL-22(-/-) mice had increased lethality, neutrophil accumulation and pro-inflammatory cytokines in tissues, notably IL-17A. Viral load was increased in spleen and liver of infected IL-22(-/-) mice. There was also more severe liver injury, as seen by increased transaminases levels and tissue histopathology. gammadelta T cells and NK cells are sources of IL-17A and IL-22, respectively, in liver and spleen. We also show that DENV-infected HepG2 cells treated with rhIL-22 had reduced cell death and decreased IL-6 production. IL-17RA(-/-) mice were protected upon infection and IL-17A-neutralizing-Ab-treatment partially reversed the phenotype observed in IL-22(-/-) -infected mice. We suggest that disrupting the balance between IL-22 and IL-17A levels may represent an important strategy to reduce inflammation and tissue injury associated with severe dengue infection. |
