IL‐22 modulates IL‐17A production and controls inflammation and tissue damage in experimental dengue infection |
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| Authors: | 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 |
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| Affiliation: | 1. Immunopharmacology, Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, , Belo Horizonte, MG, Brazil;2. Université d'Orléans and CNRS UMR 7355, Molecular and Experimental Immunology and Neurogenetics, Orléans, France and IIDMM, University of Cape Town, , Cape Town, RSA;3. Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, , Belo Horizonte, MG, Brazil;4. Instituto de Bioquimica Médica, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro (UFRJ), , Rio de Janeiro, RJ, Brazil;5. Instituto de Microbiologia Paulo de Góes, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro (UFRJ), , Rio de Janeiro, RJ, Brazil;6. Université de Poitiers, EA 4331, and Centre Hospitalier Universitaire de Poitiers, , Poitiers, France;7. Ludwig Institute for Cancer Research and Experimental Medicine Unit, de Duve Institute, Université Catholique de Louvain, , Brussels, Belgium |
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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. |
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| Keywords: | Dengue virus IL‐17A IL‐22 Infection Inflammation |
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