title: IL-22 modulates IL-17A production and controls inflammation and tissue damage in experimental dengue infection.
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.
authors.affiliation: Immunopharmacology, Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil. rguabiraba@gmail.com
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Guabiraba
authors.forename: Anne-Gaëlle
authors.initials: AG
authors.lastname: Besnard
authors.forename: Rafael E
authors.initials: RE
authors.lastname: Marques
authors.forename: Isabelle
authors.initials: I
authors.lastname: Maillet
authors.forename: Caio T
authors.initials: CT
authors.lastname: Fagundes
authors.forename: Thais M
authors.initials: TM
authors.lastname: Conceição
authors.forename: Naiara M
authors.initials: NM
authors.lastname: Rust
authors.forename: Sandrine
authors.initials: S
authors.lastname: Charreau
authors.forename: Isabelle
authors.initials: I
authors.lastname: Paris
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Lecron
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Renauld
authors.forename: Valérie
authors.initials: V
authors.lastname: Quesniaux
authors.forename: Andrea T
authors.initials: AT
authors.lastname: Da Poian
authors.forename: Luciana B
authors.initials: LB
authors.lastname: Arruda
authors.forename: Danielle G
authors.initials: DG
authors.lastname: Souza
authors.forename: Bernhard
authors.initials: B
authors.lastname: Ryffel
authors.forename: Mauro M
authors.initials: MM
authors.lastname: Teixeira
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D003715:Dengue / Q000276:immunology*; D003716:Dengue Virus / Q000276:immunology*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D056945:Hep G2 Cells; D006801:Humans; D007249:Inflammation / Q000235:genetics; D018836:Inflammation Mediators / Q000378:metabolism*; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008099:Liver / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology* / Q000821:virology; D053722:Receptors, Interleukin-17 / Q000235:genetics; D019562:Viral Load / Q000235:genetics; D000097043:Interleukin-22
chemical_list: D018836:Inflammation Mediators; D020381:Interleukin-17; D015850:Interleukin-6; D007378:Interleukins; D053722:Receptors, Interleukin-17; D000097043:Interleukin-22