IL-22 modulates IL-17A production and controls inflammation and tissue damage in experimental dengue infection

Guabiraba Brito, R. et al. (2013) IL-22 modulates IL-17A production and controls inflammation and tissue damage in experimental dengue infection. European Journal of Immunology, 43(6), pp. 1529-1544. (doi: 10.1002/eji.201243229)

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Abstract

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. γδ 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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Besnard, Dr Anne-Gaelle and Guabiraba Brito, Dr Rodrigo
Authors: Guabiraba Brito, R., Besnard, A.-G., Marques, R.E., Maillet, I., Fagundes, C.T., Conceição, T.M., Rust, N.M., Charreau, S., Paris, I., Lecron, J.-C., Renauld, J.-C., Quesniaux, V., Da Poian, A.T., Arruda, L.B., Souza, D.G., Ryffel, B., and Teixeira, M.M.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:European Journal of Immunology
Publisher:Wiley
ISSN:0014-2980
ISSN (Online):1521-4141
Published Online:17 April 2013

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