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Journal Articles Immunology Year : 2018

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

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Abstract

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.

Dates and versions

hal-02126573 , version 1 (11-05-2019)

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Rafael Marques, Anne-Gaelle Besnard, Isabelle Maillet, Caio Fagundes, Danielle Souza, et al.. Interleukin-33 contributes to disease severity in Dengue virus infection in mice. Immunology, 2018, 155 (4), pp.477-490. ⟨10.1111/imm.12988⟩. ⟨hal-02126573⟩

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