Microglia and macrophages alterations in the CNS during acute SIV infection: A single-cell analysis in rhesus macaques

PLoS Pathogens, Journal Year: 2024, Volume and Issue: 20(9), P. e1012168 - e1012168

Published: Sept. 16, 2024

Human Immunodeficiency Virus (HIV) is widely acknowledged for its profound impact on the immune system. Although HIV primarily affects peripheral CD4 T cells, influence central nervous system (CNS) cannot be overlooked. Within brain, microglia and CNS-associated macrophages (CAMs) serve as primary targets simian immunodeficiency virus (SIV) in nonhuman primates. This infection can lead to neurological effects establish a viral reservoir. Given gaps our understanding of how these cells respond vivo acute CNS infection, we conducted single-cell RNA sequencing (scRNA-seq) myeloid from brains three rhesus macaques 12 days after SIV along with uninfected controls. Our analysis revealed six distinct microglial clusters including homeostatic microglia, preactivated activated expressing high levels inflammatory disease-related molecules. In response population decreased, while increased. All exhibited upregulation MHC class I molecules interferon-related genes, indicating their crucial roles defending against during phase. also upregulated genes linked cellular senescence. Additionally, identified two CAM populations: CD14 low CD16 hi CAMs. Interestingly, dominant changed one an phenotype. Specific within macrophage cluster were associated neurodegenerative pathways, suggesting potential links neurocognitive disorders. research sheds light intricate interactions between innate responses, CNS, providing valuable insights future investigations.

Language: Английский

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Endogenous opiates and behavior: 2022

Peptides, Journal Year: 2023, Volume and Issue: 169, P. 171095 - 171095

Published: Sept. 12, 2023

Language: Английский

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Transcriptional impacts of substance use disorder and HIV on human ventral midbrain neurons and microglia

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 6, 2025

Abstract For people with HIV (PWH), substance use disorders (SUDs) are a prominent neurological risk factor, and the impacts of both on dopaminergic pathways potential point deleterious convergence. Here, we profile, at single nucleus resolution, substantia nigra (SN) transcriptomes 90 postmortem donors in context chronic opioid/cocaine SUD, including 67 prospectively characterized PWH. We report altered microglial expression for hundreds pro- anti-inflammatory regulators attributable to HIV, separately, SUD. Stepwise, progressive dysregulation, coupled SN GABAergic signaling, was associated SUD/HIV dual diagnosis further lack viral suppression blood. In virologically suppressed donors, SUD comorbidity transcriptional changes permissive infection. HIV-related downregulation monoamine reuptake transporters specifically neurons regardless status or load, additional signatures consistent selective vulnerability dopamine neurons.

Language: Английский

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CNS Viral Infections—What to Consider for Improving Drug Treatment: A Plea for Using Mathematical Modeling Approaches

CNS Drugs, Journal Year: 2024, Volume and Issue: 38(5), P. 349 - 373

Published: April 5, 2024

Neurotropic viruses may cause meningitis, myelitis, encephalitis, or meningoencephalitis. These inflammatory conditions of the central nervous system (CNS) have serious and devastating consequences if not treated adequately. In this review, we first summarize how neurotropic can enter CNS by (1) crossing blood-brain barrier blood-cerebrospinal fluid barrier; (2) invading nose via olfactory route; (3) peripheral system. then intracellular space brain cells endocytosis and/or membrane fusion. Antiviral drugs are currently used for different viral infections, even though their use dosing regimens within CNS, with exception acyclovir, minimally supported clinical evidence. We therefore provide considerations to optimize drug treatment(s) these viruses. should cross blood–brain barrier/blood cerebrospinal pass cellular inhibit inside cells. Some antiviral also require conversion into active metabolite(s). This illustrates need better understand mechanisms because processes dictate exposure that ultimately determine success infections. Finally, discuss mathematical model-based approaches optimizing treatments. Thereby emphasizing potential physiologically based pharmacokinetic models direct measurement in living humans faces ethical restrictions. Existing combined vitro pharmacokinetic/pharmacodynamic information be predict evaluate efficacy treatments

Language: Английский

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Microglia and macrophages alterations in the CNS during acute SIV infection: a single-cell analysis in rhesus macaques

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: April 4, 2024

ABSTRACT Human Immunodeficiency Virus (HIV) is widely acknowledged for its profound impact on the immune system. Although HIV primarily affects peripheral CD4 T cells, influence central nervous system (CNS) cannot be overlooked. Within brain, microglia and CNS-associated macrophages (CAMs) serve as primary targets HIV, well simian immunodeficiency virus (SIV) in nonhuman primates. This infection can lead to neurological effects establishment of a viral reservoir. Given gaps our understanding how these cells respond vivo acute CNS infection, we conducted single-cell RNA sequencing (scRNA-seq) myeloid from brains three rhesus macaques 12-days after SIV along with uninfected controls. Our analysis revealed six distinct microglial clusters including homeostatic microglia, preactivated activated expressing high levels inflammatory disease-related molecules. In response population decreased, while increased. All exhibited upregulation MHC class I molecules interferon-related genes, indicating their crucial roles defending against during phase. also upregulated genes linked cellular senescence. Additionally, identified two CAM populations: CD14 low CD16 hi CAMs. Interestingly, dominant changed one an phenotype. Notably, specific within macrophage cluster were associated neurodegenerative pathways, suggesting potential links neurocognitive disorders. research sheds light intricate interactions between innate responses, CNS, providing valuable insights future investigations. AUTHOR SUMMARY HIV’s entry into dysfunction, HIV-associated disorders (HAND), While are responses remain poorly defined. To address this, employed scRNA-seq technique study populations infection. By identifying signature different phenotypes mapping them various biological pathological discovered cell strongly other varying degrees activation among possibly mediated by signaling pathways. developed signs senescence pathway. These findings shed immunological brain therapeutic strategies targeting this critical stage aiming eliminate

Language: Английский

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Beyond the Syndemic of Opioid Use Disorders and HIV: The Impact of Opioids on Viral Reservoirs

Viruses, Journal Year: 2023, Volume and Issue: 15(8), P. 1712 - 1712

Published: Aug. 9, 2023

People with HIV are more likely to have opioid use disorder and be prescribed opioids for chronic pain than the general population; however, effects of on immune system persistence not been fully elucidated. Opioids may affect reservoirs during their establishment, maintenance, reactivation by enhancing infectivity replication due upregulation co-receptors impairment innate antiviral responses. also modulate cell functioning microbial translocation can reverse viral latency. In this review, we summarize current findings against modulating cellular anatomical reservoirs, highlighting limitations that in vitro, ex vivo, vivo studies field. We propose further research targets potential strategies approach topic.

Language: Английский

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Inflammation-Associated Lung Tissue Remodeling and Fibrosis in Morphine-Dependent SIV-Infected Macaques

American Journal Of Pathology, Journal Year: 2023, Volume and Issue: 193(4), P. 380 - 391

Published: March 30, 2023

Language: Английский

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Primary Literature for Teaching Neuroimmunology – An Instructor's Resource

Journal of Undergraduate Neuroscience Education, Journal Year: 2024, Volume and Issue: 23(1), P. 1 - 4

Published: Dec. 1, 2024

Supplementing textbooks with primary literature in teaching neuroscience is a growing practice associated several positive outcomes, such as increased content knowledge, research and data skills, critical thinking. This pedagogical approach, however, still needs further development to make it accessible instructors valuable students. article describes series of published articles we used an undergraduate neuroimmunology course. Articles were selected supplement the significant principles disease neuro-infections, autoimmune diseases, neurodegenerative diseases. Specifically, on multiple sclerosis, experimental encephalitis, Herpes Simplex Virus 1, SIV/HIV infections, Alzheimer’s, Parkinson’s diseases are described, value each enunciated. These sources could be incorporated into range graduate courses introduce topics neuroimmunology.

Language: Английский

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Immune response and cytokine profiles in post-laminectomy pain syndrome: comparative analysis after treatment with intrathecal opioids, oral opioids, and non-opioid therapies

Inflammopharmacology, Journal Year: 2024, Volume and Issue: 32(5), P. 3295 - 3309

Published: July 22, 2024

Language: Английский

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Rise of Macaque Models for Immunity and Infection Research

NeuroImmune Pharmacology and Therapeutics, Journal Year: 2024, Volume and Issue: unknown, P. 71 - 91

Published: Jan. 1, 2024

Language: Английский

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