ArticleJournal of neuroinflammation2016
IL-33 signaling is essential to attenuate viral-induced encephalitis development by downregulating iNOS expression in the central nervous system.
Article in Journal of neuroinflammation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 40 citations in OpenAlex.
- Tiny needles, major benefits: acupuncture in child health.BMC pediatrics · 2025Article
- Oligodendrocyte-derived IL-33 functions as a microglial survival factor during neuroinvasive flavivirus infection.PLoS pathogens · 2023Article
- Interleukins, Chemokines, and Tumor Necrosis Factor Superfamily Ligands in the Pathogenesis of West Nile Virus Infection.Viruses · 2023Review
- Interrelationship and Sequencing of Interleukins4, 13, 31, and 33 - An Integrated Systematic Review: Dermatological and Multidisciplinary Perspectives.Journal of inflammation research · 2022Review
- IL-33 promotes innate lymphoid cell-dependent IFN-γ production required for innate immunity toeLife · 2021Article
- Therapeutic Opportunities of Interleukin-33 in the Central Nervous System.Frontiers in immunology · 2021Review
- IL-33/ST2 axis is involved in disease progression in the spleen during Leishmania donovani infection.Parasites & vectors · 2020Article
- CCR2 Plays a Protective Role in Rocio Virus-Induced Encephalitis by Promoting Macrophage Infiltration Into the Brain.The Journal of infectious diseases · 2019Article
- Impact of mast cells in depression disorder: inhibitory effect of IL-37 (new frontiers).Immunologic research · 2018Review
- Expression and Function of IL-33/ST2 Axis in the Central Nervous System Under Normal and Diseased Conditions.Frontiers in immunology · 2018Review
- Interferons in Traumatic Brain and Spinal Cord Injury: Current Evidence for Translational Application.Frontiers in neurology · 2018Review
- Splenic macrophages are required for protective innate immunity against West Nile virus.PloS one · 2018Article
- Regulatory T cell frequency, but not plasma IL-33 levels, represents potential immunological biomarker to predict clinical response to intravenous immunoglobulin therapy.Journal of neuroinflammation · 2017Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundViral encephalitis is a common cause of lethal infections in humans, and several different viruses are documented to be responsible. Rocio virus is a flavivirus that causes a severe lethal encephalitis syndrome in humans and also mice, providing an interesting model to study the CNS compartmentalized immune response. Interleukin 33 (IL-33), a member of the IL-1 family, is an immunomodulatory cytokine that is highly expressed in the CNS. However, the role of IL-33 on viral encephalitis remains unclear. Therefore, we aimed to explore how the IL-33/ST2 axis regulates the local immune response during Rocio virus infection.
methodsWild-type (WT), ST2 (ST2(-/-)), and nitric oxide synthase-deficient mice (iNOS(-/-)) and Stat6 (Stat6(-/-))-deficient mice were infected with different concentrations of the Rocio virus by intraperitoneal route, the cytokine mRNA level in CNS was analyzed by qPCR, and cellular immunophenotyping was performed on infected mice by the flow cytometry of isolated CNS mononuclear cells.
resultsWe have shown that the mRNA expression of IL-33 and ST2 receptors is increased in the CNS of Rocio virus-infected WT mice and that ST2(-/-) mice showed increased susceptibility to infection. ST2 deficiency was correlated with increased tissue pathology, cellular infiltration, and tumor necrosis factor alpha (TNF-α) and interferon-gamma (IFN-γ) mRNA levels and higher viral load in the CNS, compared with wild-type mice. The increased Th1 cytokine levels released in the CNS acted on infiltrating macrophages, as evidenced by flow cytometry characterization of cellular infiltrates, inducing the expression of iNOS, contributing to brain injury. Moreover, iNOS(-/-) mice were more resistant to Rocio virus encephalitis, presenting a lower clinical score and reduced mortality rate, despite the increased tissue pathology.
conclusionsWe provide evidences of a specific role for IL-33 receptor signaling in nitric oxide induction through local IFN-γ modulation, suggesting that nitric oxide overproduction might have an important role in the progression of experimental viral encephalitis.
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