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Journal article
Inflammatory microglia signals drive A1-like polarization of astrocytes even in the presence of HIV-1 Tat
Molecular neurobiology, v 63(1), 251
2026
PMID: 41345807
Featured in Collection : Research Supported by Drexel Libraries' OA Programs
Abstract
In the context of neurodegeneration, activated microglia facilitate inflammation via secretion of TNF-α, IL-1α, and C1q. Astrocytes exposed to this signaling array polarize to a reactive inflammatory phenotype, termed A1 or A1-like. Astrocytes are essential for neuronal survival, synaptic support, and blood–brain barrier (BBB) function, but A1-like astrocytes upregulate inflammatory gene expression, downregulate neurotrophic factors, and secrete neurotoxic signals. The consequences of A1-like polarization on BBB function are unknown but may have etiological implications for some diseases. Frequently identified by upregulation of complement component 3 (C3), A1-like astrocytes have been characterized in neurodegenerative disorders like Alzheimer’s disease, with polarization correlated with disease progression and severity. However, the role of A1-like astrocytes in neurodegeneration associated with chronic viral infections, like HIV-1-associated neurocognitive disorder (HAND), remains unclear. An in vitro system using primary human astrocytes, as well as a BBB model featuring primary human brain microvascular endothelial cells (BMECs) co-cultured with astrocytes, was used to elucidate cellular and molecular consequences of chronic astrocyte activation. As measured by whole transcriptome analysis and protein expression assays, repeated treatment with TNF-α, IL-1α, and C1q induced A1-like polarization of astrocytes both in monoculture and in a BBB model, resulting in increased secretion of pro-inflammatory signals. No substantial change to BBB permeability was observed. In contrast, exposure to HIV-1 viral protein Tat did not independently induce A1-like polarization. Ongoing investigations into the effect of astrocyte polarization on BBB integrity and treatment with pathogenic proteins may provide insights into the role of neurotoxic astrocytes in neurovirologic pathologies.
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Details
- Title
- Inflammatory microglia signals drive A1-like polarization of astrocytes even in the presence of HIV-1 Tat
- Creators
- Jill M Lawrence - Drexel University, Microbiology and ImmunologyWilliam Nathanial Dampier - Drexel University, Microbiology and ImmunologyJoshua Chang Mell - Drexel University, Microbiology and ImmunologyDiehl Remedio De Souza - Drexel University, Microbiology and ImmunologyKayla Anne Schardien - Drexel University, Neurobiology and AnatomyKyle C Yeakle - Drexel University, Biochemistry and Molecular BiologyR. Jordan Barnett - Drexel University, Microbiology and ImmunologyBhaswati Sen - Drexel University, College of MedicineAzad I Ahmed - Drexel University, Microbiology and ImmunologyMichael Bouchard - Drexel University, Biochemistry and Molecular BiologyBrian Wigdahl - Drexel University, Microbiology and ImmunologyMichael R Nonnemacher (Corresponding Author) - Drexel University, Microbiology and Immunology
- Publication Details
- Molecular neurobiology, v 63(1), 251
- Publisher
- Springer Nature
- Number of pages
- 24
- Grant note
- National Institute of Neurological Disorders and Stroke: NS089435 National Institute of Mental Health: MH079785
The authors were funded in part by the Public Health Service, National Institutes of Health, through grants from the National Institute of Neurological Disorders and Stroke (NINDS) R01 NS089435 (PI, Michael R. Nonnemacher). The contents of the paper are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology; Microbiology and Immunology; College of Medicine
- Web of Science ID
- WOS:001631046900001
- Scopus ID
- 2-s2.0-105023912307
- Other Identifier
- 991022135141804721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Neurosciences