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

Marques, R. E., Besnard, A.-G., Maillet, I., Fagundes, C. T., Souza, D. G., Ryffel, B., Teixeira, M. M., Liew, F. Y. and Guabiraba, R. (2018) Interleukin-33 contributes to disease severity in Dengue virus infection in mice. Immunology, 155(4), pp. 477-490. (doi: 10.1111/imm.12988) (PMID:30098206)

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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. Interleukin‐33 (IL‐33) is a pleiotropic cytokine with pro‐inflammatory effects whose role in dengue has not been fully elucidated. 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 with 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 with wild‐type 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, probably 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.

Item Type:Articles
Additional Information:This work was supported by the Institut National de la Recherche Agronomique (INRA, France), the Wellcome Trust and the Medical Research Council (UK), the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Brazil) and the Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG, Brazil).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Liew, Prof Foo
Authors: Marques, R. E., Besnard, A.-G., Maillet, I., Fagundes, C. T., Souza, D. G., Ryffel, B., Teixeira, M. M., Liew, F. Y., and Guabiraba, R.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Immunology
Publisher:Wiley
ISSN:0019-2805
ISSN (Online):1365-2567
Published Online:11 August 2018

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