RGD Reference Report - Interleukin-33 contributes to disease severity in Dengue virus infection in mice. - Rat Genome Database

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

Authors: Marques, Rafael E  Besnard, Anne-GaĆ«lle  Maillet, Isabelle  Fagundes, Caio T  Souza, Danielle G  Ryffel, Bernhard  Teixeira, Mauro M  Liew, Foo Y  Guabiraba, Rodrigo 
Citation: Marques RE, etal., Immunology. 2018 Dec;155(4):477-490. doi: 10.1111/imm.12988. Epub 2018 Sep 10.
RGD ID: 39938828
Pubmed: (View Article at PubMed) PMID:30098206
DOI: Full-text: DOI:10.1111/imm.12988

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.

Annotation

Disease Annotations    
dengue disease  (IDA,IMP,ISO)

Objects Annotated

Genes (Rattus norvegicus)
Cxcr2  (C-X-C motif chemokine receptor 2)
Il1rl1  (interleukin 1 receptor-like 1)
Il33  (interleukin 33)

Genes (Mus musculus)
Cxcr2  (chemokine (C-X-C motif) receptor 2)
Il1rl1  (interleukin 1 receptor-like 1)
Il33  (interleukin 33)

Genes (Homo sapiens)
CXCR2  (C-X-C motif chemokine receptor 2)
IL1RL1  (interleukin 1 receptor like 1)
IL33  (interleukin 33)


Additional Information