Modulation of host immunity by sensory neurons

Trends in Immunology, Journal Year: 2024, Volume and Issue: 45(5), P. 381 - 396

Published: May 1, 2024

Recent studies have uncovered a new role for sensory neurons in influencing mammalian host immunity, challenging conventional notions of the nervous and immune systems as separate entities. In this review we delve into groundbreaking paradigm neuroimmunology discuss recent scientific evidence impact on responses against wide range pathogens diseases, encompassing microbial infections cancers. These valuable insights enhance our understanding interactions between systems, also pave way developing candidate innovative therapeutic interventions immune-mediated diseases highlighting importance interdisciplinary research field.

Language: Английский

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Experience-dependent MAPK/ERK signaling in glia regulates critical period remodeling of synaptic glomeruli

Cellular Signalling, Journal Year: 2024, Volume and Issue: 120, P. 111224 - 111224

Published: May 12, 2024

Early-life critical periods allow initial sensory experience to remodel brain circuitry so that synaptic connectivity can be optimized environmental input. In the Drosophila juvenile brain, olfactory neuron (OSN) glomeruli are pruned by glial phagocytosis in dose-dependent response early odor during a well-defined period. Extracellular signal-regulated kinase (ERK) separation of phases-based activity reporter (SPARK) biosensors reveal experience-dependent signaling glia this Glial ERK-SPARK is depressed removal Draper receptors orchestrating phagocytosis. Cell-targeted genetic knockdown ERK reduces pruning OSN mechanism. Noonan Syndrome caused gain-of-function mutations protein tyrosine phosphatase non-receptor type 11 (PTPN11) inhibiting signaling, and glial-targeted patient-derived mutation increases impairs glomeruli. We conclude period drives required for glomeruli, altered mechanism disease model.

Language: Английский

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Glioblastoma microenvironment—from biology to therapy

Genes & Development, Journal Year: 2024, Volume and Issue: unknown

Published: May 29, 2024

Glioblastoma (GBM) is the most aggressive primary brain cancer. These tumors exhibit high intertumoral and intratumoral heterogeneity in neoplastic nonneoplastic compartments, low lymphocyte infiltration, abundance of myeloid subsets that together create a highly protumorigenic immunosuppressive microenvironment. Moreover, heterogeneous GBM cells infiltrate adjacent tissue, remodeling neural microenvironment to foster tumor electrochemical coupling with neurons metabolic astrocytes, thereby driving growth. Here, we review its role low-to-high-grade glioma transition, concluding discussion challenges therapeutically targeting outlining future research opportunities.

Language: Английский

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Effects of Antiretroviral Treatment on Central and Peripheral Immune Response in Mice with EcoHIV Infection

Cells, Journal Year: 2024, Volume and Issue: 13(10), P. 882 - 882

Published: May 20, 2024

HIV infection is an ongoing global health issue, despite increased access to antiretroviral therapy (ART). People living with (PLWH) who are virally suppressed through ART still experience negative outcomes, including neurocognitive impairment. It increasingly evident that may act independently or in combination alter the immune state, though this difficult disentangle clinical population. Thus, these experiments used multiplexed chemokine/cytokine arrays assess peripheral (plasma) and brain (nucleus accumbens; NAc) expression of targets presence absence treatment EcoHIV mouse model. The findings identify effects bictegravir (B), emtricitabine (F), tenofovir alafenamide (TAF) on numerous targets. In NAc, included EcoHIV-induced increases IL-1α IL-13 B/F/TAF-induced reductions KC/CXCL1. periphery, IL-6 LIF expression, while B/F/TAF reduced IL-12p40 expression. ART, IBA-1 was negatively correlated CX3CL1 NAc EcoHIV-infected mice. These distinct central factors emphasize need consider neural outcomes.

Language: Английский

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Microglial Engulfment of Multisensory Terminals in the Midbrain Inferior Colliculus During an Early Critical Period

The Journal of Comparative Neurology, Journal Year: 2025, Volume and Issue: 533(3)

Published: March 1, 2025

The lateral cortex of the inferior colliculus (LCIC) receives multisensory input arrays that preferentially target its compartmental organization. Inputs somatosensory origin end within modular zones, while auditory inputs terminate throughout an encompassing matrix. Such discrete mapping emerges during early postnatal critical period (birth to day 12, P12) via a process segregation. Similar other primitive brain maps, it appears initial excess connections may be pruned through refinement process. Microglial cells (MGCs) are involved in variety systems selective removal and degradation unnecessary contacts. Aberrations map plasticity periods have been associated with certain neurodevelopmental conditions, including autism spectrum disorders (ASD). Despite evidence linking integration deficits cognitive/behavioral disturbances ASD, mechanisms govern multimodal network modifications remain poorly understood. Thus, present study combines novel tract-tracing approaches living preparations immunocytochemistry CX3CR1-GFP knock-in mice determine: (1) if fractalkine signaling (CX3CL1-CX3CR1) influences MGC engulfment afferents, (2) whether individual MGCs phagocytose endings (auditory somatosensory), (3) consumed product is degraded MGC's lysosomal pathway. We demonstrate active pruning at peak LCIC stages for projection shaping (P4, P8) significantly decreases coincident closure (P12). While developmentally regulated, signaling-independent. also provide microglia engulf both terminals co-localize marker, CD68. These results suggest prominent role remodeling midbrain maps.

Language: Английский

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Tryptophan Metabolism Through the Kynurenine Pathway in Glial Cells

Neuroglia, Journal Year: 2025, Volume and Issue: 6(1), P. 14 - 14

Published: March 12, 2025

The central nervous system (CNS) relies on complex and dynamic interactions between neurons glial cells. Among cells, astrocytes regulate the chemical environment surrounding supply essential nutrients for brain metabolism whereas microglia, resident macrophages of CNS, play critical roles in homeostasis, defense, responses to injury. Both microglia contribute regulation excitotoxicity inflammation mediated by tryptophan (Trp) via kynurenine pathway. Trp generates several bioactive metabolites, including quinolinic acid (QUIN) kynurenic (KYNA), which have opposing effects. QUIN, produced activated acts as an agonist NMDA receptors; excessive stimulation these receptors can lead neuronal death. Conversely, KYNA, primarily 2,3-aminotransferases (KAT), receptor antagonist, conferring neuroprotection mitigating excitotoxicity. Dysregulation is implicated many neurodegenerative diseases such Alzheimer’s disease, Parkinson’s multiple sclerosis amyotrophic lateral sclerosis, well various neuropsychiatric disorders. This review examines cellular molecular mechanisms underlying highlighting unique contributions each phenotype, implications CNS pathologies, potential biomarkers therapeutic targets restoring homeostasis preventing disease progression.

Language: Английский

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How microglia contribute to the induction and maintenance of neuropathic pain

Nature reviews. Neuroscience, Journal Year: 2025, Volume and Issue: unknown

Published: March 24, 2025

Language: Английский

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Potential roles for microglia in drug addiction: Adolescent neurodevelopment and beyond

Journal of Neuroimmunology, Journal Year: 2025, Volume and Issue: unknown, P. 578600 - 578600

Published: March 1, 2025

Language: Английский

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Emerging roles of antimicrobial peptides in innate immunity, neuronal function, and neurodegeneration

Trends in Neurosciences, Journal Year: 2024, Volume and Issue: 47(11), P. 949 - 961

Published: Oct. 9, 2024

Language: Английский

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Effects of antiretroviral treatment on central and peripheral immune response in mice with EcoHIV infection

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

Published: April 14, 2024

Abstract HIV infection is an ongoing global health issue despite increased access to antiretroviral therapy (ART). People living with (PLWH) who are virally suppressed through ART still experience negative outcomes, including neurocognitive impairment. It increasingly evident that may act independently or in combination alter immune state, though this difficult disentangle the clinical population. Thus, these experiments used multiplexed chemokine/cytokine arrays assess peripheral (plasma) and brain (nucleus accumbens; NAc) expression of targets presence absence treatment EcoHIV mouse model. The findings identify effects bictegravir (B), emtricitabine (F) tenofovir alafenamide (TAF) on numerous targets. In NAc, included EcoHIV-induced increases IL-1α IL-13 B/F/TAF-induced reductions KC/CXCL1. periphery, IL-6 LIF expression, while B/F/TAF reduced IL-12p40 expression. ART, IBA-1 was negatively correlated CX3CL1 NAc EcoHIV-infected mice. These distinct central factors emphasize need consider neural outcomes.

Language: Английский

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