Interleukin-33 contributes to disease severity in Dengue virus infection in mice

Autor: Mauro M. Teixeira, Danielle G. Souza, Isabelle Maillet, Foo Y. Liew, Anne-Gaelle Besnard, Rafael Elias Marques, Caio T. Fagundes, Bernhard Ryffel, Rodrigo Guabiraba
Přispěvatelé: Institute of Infection, Immunity and Inflammation, Glasgow Biomedical Research Centre, University of Glasgow, Immunologie et Neurogénétique Expérimentales et Moléculaires (INEM), Centre National de la Recherche Scientifique (CNRS)-Université d'Orléans (UO), Immunologie et Embryologie Moléculaires (IEM), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), INRA, (France), Wellcome Trust, Medical Research Council (UK), Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq, Brazil), Fundacao de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG, Brazil), programme INCT em Dengue (CNPq, Brazil)
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: Immunology
Immunology, Wiley, 2018, 155 (4), pp.477-490. ⟨10.1111/imm.12988⟩
ISSN: 0019-2805
1365-2567
Popis: International audience; The excessive inflammation often present in patients with severe dengue infection is considered both a hallmark of disease and a target for potential treatments. IL-33 is a pleiotropic cytokine with pro-inflammatory effects whose role in dengue has not been fully elucidated. Here we demonstrate that IL-33 plays a disease-exacerbating role during experimental dengue infection in immunocompetent mice. Mice infected with Dengue virus serotype 2 (DENV2) produced high levels of IL-33. DENV2-infected mice treated with recombinant IL-33 developed markedly more severe disease compared to untreated mice as assessed by mortality, granulocytosis, liver damage and pro-inflammatory cytokine production. Conversely, ST2-/- mice (deficient in IL-33 receptor) infected with DENV2 developed significantly less severe disease compared to wild-type (WT) mice. Furthermore, the increased disease severity and the accompanying pathology induced by IL-33 during dengue infection were reversed by the simultaneous treatment with a CXCR2 receptor antagonist (DF2156A). Together, these results indicate that IL-33 plays a disease-exacerbating role in experimental dengue infection, likely driven by CXCR2-expressing cells, leading to elevated pro-inflammatory response-mediated pathology. Our results also indicate that IL-33 is a potential therapeutic target for dengue infection.
Databáze: OpenAIRE
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