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

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.

• Authors: Rafael E Marques, Anne-Gaëlle Besnard, Isabelle Maillet, Caio T Fagundes, Danielle G Souza, Bernhard Ryffel, Mauro M Teixeira, Foo Y Liew, Rodrigo Guabiraba
• Journal: Immunology (Immunology) Vol. 155 Issue 4 Pg. 477-490 (12 2018) ISSN: 1365-2567 [Electronic] England
• PMID: 30098206 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 John Wiley & Sons Ltd.

Chemical References

• 2'-((4'-trifluoromethanesulfonyloxy)phenyl)-N-methanesulfonylpropionamide
• Il33 protein, mouse
• Interleukin-1 Receptor-Like 1 Protein
• Interleukin-33
• Receptors, Interleukin-8B
• Recombinant Proteins
• Sulfonamides

Topics

• Animals
• Dengue (immunology, virology)
• Dengue Virus (immunology)
• Disease Progression
• Interleukin-1 Receptor-Like 1 Protein (deficiency, genetics)
• Interleukin-33 (pharmacology)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Receptors, Interleukin-8B (antagonists & inhibitors)
• Recombinant Proteins (pharmacology)
• Sulfonamides (pharmacology)