ArticleJournal of neuroinflammation2021
High-parameter cytometry unmasks microglial cell spatio-temporal response kinetics in severe neuroinflammatory disease.
Article in Journal of neuroinflammation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 2 of them syntheses that pooled it.
What it found
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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.
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Who cites it
21 citing papers in PubMed, 2 syntheses or guidelines pooled it, 30 citations in OpenAlex.
- Pooled it
- Experimental procedures for flow cytometry of wild-type mouse brain: a systematic review.Frontiers in immunology · 2023Pooled it
- A characterisation of the immune cells in immunocompetent and immunodeficient mice with orthotopic brain tumors.Clinical & translational immunology · 2026Article
- Interplay between Peripheral and Central Nervous System Myeloid Cells during Aging: Impact for Lade-Life Depression and Alzheimer's Disease.Neuroimmunomodulation · 2026Review
- High Fat Low Carbohydrate Diet Is Linked to CNS Autoimmunity Protection.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- NLRP3 activation induces BBB disruption and neutrophil infiltration via CXCR2 signaling in the mouse brain.Journal of neuroinflammation · 2025Article
- Sex-specific regulation of microglial MyD88 in HMGB1-Induced anxiety phenotype in mice.Neurobiology of stress · 2025Article
- Leukocyte recruitment in flavivirus-induced encephalitis.Frontiers in immunology · 2025Review
- Sentinels of neuroinflammation: the crucial role of myeloid cells in the pathogenesis of gliomas and neurodegenerative diseases.Journal of neuroinflammation · 2024Review
- MAVS signaling shapes microglia responses to neurotropic virus infection.Journal of neuroinflammation · 2024Article
- Assessing Extracellular Vesicles in Human Biofluids Using Flow-Based Analyzers.Advanced healthcare materials · 2023Article
- Detection of disease-associated microglia among various microglia phenotypes induced by West Nile virus infection in mice.Journal of neurovirology · 2023Article
- Advances in proteomic phenotyping of microglia in neurodegeneration.Proteomics · 2023Review
- Putting PLX5622 into perspective: microglia in central nervous system viral infection.Neural regeneration research · 2023Article
- Temporal tracking of microglial and monocyte single-cell transcriptomics in lethal flavivirus infection.Acta neuropathologica communications · 2023Article
- Article
- Live imaging of microglia during sleeping sickness reveals early and heterogeneous inflammatory responses.Frontiers in immunology · 2023Article
- Clodronate is not protective in lethal viral encephalitis despite substantially reducing inflammatory monocyte infiltration in the CNS.Frontiers in immunology · 2023Article
- Microglia and monocytes in inflammatory CNS disease: integrating phenotype and function.Acta neuropathologica · 2022Review
- PLX5622 Reduces Disease Severity in Lethal CNS Infection by Off-Target Inhibition of Peripheral Inflammatory Monocyte Production.Frontiers in immunology · 2022Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
backgroundDifferentiating infiltrating myeloid cells from resident microglia in neuroinflammatory disease is challenging, because bone marrow-derived inflammatory monocytes infiltrating the inflamed brain adopt a 'microglia-like' phenotype. This precludes the accurate identification of either cell type without genetic manipulation, which is important to understand their temporal contribution to disease and inform effective intervention in its pathogenesis. During West Nile virus (WNV) encephalitis, widespread neuronal infection drives substantial CNS infiltration of inflammatory monocytes, causing severe immunopathology and/or death, but the role of microglia in this remains unclear.
methodsUsing high-parameter cytometry and dimensionality-reduction, we devised a simple, novel gating strategy to identify microglia and infiltrating myeloid cells during WNV-infection. Validating our strategy, we (1) blocked the entry of infiltrating myeloid populations from peripheral blood using monoclonal blocking antibodies, (2) adoptively transferred BM-derived monocytes and tracked their phenotypic changes after infiltration and (3) labelled peripheral leukocytes that infiltrate into the brain with an intravenous dye. We demonstrated that myeloid immigrants populated only the identified macrophage gates, while PLX5622 depletion reduced all 4 subsets defined by the microglial gates.
resultsUsing this gating approach, we identified four consistent microglia subsets in the homeostatic and WNV-infected brain. These were P2RY12
conclusionsOur approach enables detailed kinetic analysis of resident vs infiltrating myeloid cells in a wide range of neuroinflammatory models without non-physiological manipulation. This will more clearly inform potential therapeutic approaches that specifically modulate these cells.
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Registered trials
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.