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Complement C1q-dependent engulfment of alpha-synuclein induces ENS-resident macrophage exhaustion and accelerates Parkinson's-like gut pathology.
bioRxiv
October 2023
Department of Neuroscience, University of Florida College of Medicine. Gainesville, FL, 32610.
Deposition of misfolded α-synuclein (αsyn) in the enteric nervous system (ENS) is found in multiple neurodegenerative diseases. It is hypothesized that ENS synucleinopathy contributes to both the pathogenesis and non-motor morbidity in Parkinson's Disease (PD), but the cellular and molecular mechanisms that shape enteric histopathology and dysfunction are poorly understood. Here, we demonstrate that ENS-resident macrophages, which play a critical role in maintaining ENS homeostasis, initially respond to enteric neuronal αsyn pathology by upregulating machinery for complement-mediated engulfment.
View Article and Find Full Text PDFVancomycin-induced gut microbial dysbiosis alters enteric neuron-macrophage interactions during a critical period of postnatal development.
Front Immunol
October 2023
Division of Gastroenterology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, United States.
Vancomycin is a broad-spectrum antibiotic widely used in cases of suspected sepsis in premature neonates. While appropriate and potentially lifesaving in this setting, early-life antibiotic exposure alters the developing microbiome and is associated with an increased risk of deadly complications, including late-onset sepsis (LOS) and necrotizing enterocolitis (NEC). Recent studies show that neonatal vancomycin treatment disrupts postnatal enteric nervous system (ENS) development in mouse pups, which is in part dependent upon neuroimmune interactions.
View Article and Find Full Text PDFThe Yin/Yang Balance of Communication between Sensory Neurons and Macrophages in Traumatic Peripheral Neuropathic Pain.
Int J Mol Sci
October 2022
Department of Anatomy, Animal Physiology and Biophysics, Faculty of Biology, University of Bucharest, 91-95 Splaiul Independentei, District 5, 050095 Bucharest, Romania.
Traumatic peripheral neuropathic pain is a complex syndrome caused by a primary lesion or dysfunction of the peripheral nervous system. Secondary to the lesion, resident or infiltrating macrophages proliferate and initiate a cross-talk with the sensory neurons, at the level of peripheral nerves and sensory ganglia. The neuron-macrophage interaction, which starts very early after the lesion, is very important for promoting pain development and for initiating changes that will facilitate the chronicization of pain, but it also has the potential to facilitate the resolution of injury-induced changes and, consequently, promote the reduction of pain.
View Article and Find Full Text PDFMapping secretome-mediated interaction between paired neuron-macrophage single cells.
Proc Natl Acad Sci U S A
November 2022
Department of Biotechnology, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.
Neuron-immune interaction through secreted factors contributes significantly to the complex microenvironment in the central nervous system that could alter cell functionalities and fates in both physiological and pathological conditions, which remains poorly characterized at the single-cell level. Herein, using a spatially patterned antibody barcode microchip, we realized the mapping of 12 different secretomes, covering cytokines, neurotrophic factors (NFs), and neuron-derived exosomes (NDEs) from high-throughput, paired single cells (≥ 600) simultaneously under normal conditions and an Alzheimer's disease (AD) model induced with amyloid beta protein 1-42 (Aβ). We applied the platform to analyze the secretion profiles from paired neuron-macrophage and neuron-microglia single cells with human cell lines.
View Article and Find Full Text PDFNanogel-mediated delivery of oncomodulin secreted from regeneration-associated macrophages promotes sensory axon regeneration in the spinal cord.
Theranostics
August 2022
Department of Brain Science, Ajou University Graduate School of Medicine, Suwon, 16499, Republic of Korea.
Preconditioning nerve injury enhances axonal regeneration of dorsal root ganglia (DRG) neurons in part by driving pro-regenerative perineuronal macrophage activation. How these macrophages influence the neuronal capacity of axon regeneration remains elusive. We report that oncomodulin (ONCM) is produced from the regeneration-associated macrophages and strongly influences regeneration of DRG sensory axons.
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