ArticleASN neuro2012
Complexity of the microglial activation pathways that drive innate host responses during lethal alphavirus encephalitis in mice.
Article in ASN neuro, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.
- Frequency and Focus of in Vitro Studies of Microglia-Expressed Cytokines in Response to Viral Infection: A Systematic Review.Cellular and molecular neurobiology · 2024Pooled it
- Interferon-β Modulates Early Viral Replication Kinetics and Innate Responses to Non-Fatal Alphavirus Encephalomyelitis.Pathogens (Basel, Switzerland) · 2026Article
- Distinct Cellular Tropism and Immune Responses to Alphavirus Infection.Annual review of immunology · 2022Review
- Review
- Interferon regulatory factors 3 and 7 have distinct roles in the pathogenesis of alphavirus encephalomyelitis.The Journal of general virology · 2019Article
- Genetic control of alphavirus pathogenesis.Mammalian genome : official journal of the International Mammalian Genome Society · 2018Review
- Innate immune control of alphavirus infection.Current opinion in virology · 2018Review
- Chemokine Receptor Ccr7 Restricts Fatal West Nile Virus Encephalitis.Journal of virology · 2017Article
- Protective Effects of Glutamine Antagonist 6-Diazo-5-Oxo-l-Norleucine in Mice with Alphavirus Encephalomyelitis.Journal of virology · 2016Article
- Regulated Production of CXCL13 within the Central Nervous System.Journal of clinical & cellular immunology · 2016Article
- MicroRNA-34a Negatively Regulates Efferocytosis by Tissue Macrophages in Part via SIRT1.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- Endogenous adaptation to low oxygen modulates T-cell regulatory pathways in EAE.Journal of neuroinflammation · 2016Article
- Unc93b1 -Dependent Endosomal Toll-Like Receptor Signaling Regulates Inflammation and Mortality during Coxsackievirus B3 Infection.Journal of innate immunity · 2015Article
- Differentiation of neurons restricts Arbovirus replication and increases expression of the alpha isoform of IRF-7.Journal of virology · 2015Article
- Activation of intrinsic immune responses and microglial phagocytosis in an ex vivo spinal cord slice culture model of West Nile virus infection.Journal of virology · 2014Article
- Buggy Creek virus (Togaviridae: Alphavirus) upregulates expression of pattern recognition receptors and interferons in House Sparrows (Passer domesticus).Vector borne and zoonotic diseases (Larchmont, N.Y.) · 2014Article
- An attenuating mutation in a neurovirulent Sindbis virus strain interacts with the IPS-1 signaling pathway in vivo.Virology · 2013Article
- An ENU-induced splicing mutation reveals a role for Unc93b1 in early immune cell activation following influenza A H1N1 infection.Genes and immunityArticle
- Targeting CXCL13 During Neuroinflammation.Advances in neuroimmune biologyArticle
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Microglia express multiple TLRs (Toll-like receptors) and provide important host defence against viruses that invade the CNS (central nervous system). Although prior studies show these cells become activated during experimental alphavirus encephalitis in mice to generate cytokines and chemokines that influence virus replication, tissue inflammation and neuronal survival, the specific PRRs (pattern recognition receptors) and signalling intermediates controlling microglial activation in this setting remain unknown. To investigate these questions directly in vivo, mice ablated of specific TLR signalling molecules were challenged with NSV (neuroadapted Sindbis virus) and CNS viral titres, inflammatory responses and clinical outcomes followed over time. To approach this problem specifically in microglia, the effects of NSV on primary cells derived from the brains of wild-type and mutant animals were characterized in vitro. From the standpoint of the virus, microglial activation required viral uncoating and an intact viral genome; inactivated virus particles did not elicit measurable microglial responses. At the level of the target cell, NSV triggered multiple PRRs in microglia to produce a broad range of inflammatory mediators via non-overlapping signalling pathways. In vivo, disease survival was surprisingly independent of TLR-driven responses, but still required production of type-I IFN (interferon) to control CNS virus replication. Interestingly, the ER (endoplasmic reticulum) protein UNC93b1 facilitated host survival independent of its known effects on endosomal TLR signalling. Taken together, these data show that alphaviruses activate microglia via multiple PRRs, highlighting the complexity of the signalling networks by which CNS host responses are elicited by these infections.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.