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

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

European journal of immunology (2013-03-19)
Rodrigo Guabiraba, Anne-Gaëlle Besnard, Rafael E Marques, Isabelle Maillet, Caio T Fagundes, Thais M Conceição, Naiara M Rust, Sandrine Charreau, Isabelle Paris, Jean-Claude Lecron, Jean-Christophe Renauld, Valérie Quesniaux, Andrea T Da Poian, Luciana B Arruda, Danielle G Souza, Bernhard Ryffel, Mauro M Teixeira
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.

MATERIALS
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Product Description

Sigma-Aldrich
Anti-Dengue Virus Type II Antibody, clone 3H5-1, clone 3H5-1, Chemicon®, from mouse