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Effect of peripherally-derived macrophages in adult microglia (mouse cells)

ABSTRACT: Infiltrating monocyte derived macrophages (MDMs) and resident microglia dominate CNS injury sites. We show that MDMs and microglia can directly communicate to modulate each other’s function. Also, the presence of MDMs in CNS injury suppresses microglia-mediated phagocytosis and inflammation. We suggest that macrophages infiltrating the injured CNS provide a mechanism to control acute and chronic microglia-mediated inflammation, which could otherwise drive damage in a variety of CNS conditions. To understand the global effects of macrophage communication to microglia, we transcriptionally profiled activated adult mouse microglia in the presence or absence of macrophages with and without an inflammatory stiumulus (LPS)

ORGANISM(S): Mus musculus

PROVIDER: GSE102482 | GEO | 2018/08/01

REPOSITORIES: GEO

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Microglia coordinate cellular interactions during spinal cord repair

Project description:Traumatic spinal cord injury (SCI) triggers a neuro-inflammatory response dominated by tissue-resident microglia and monocyte derived macrophages (MDMs). Since activated microglia and MDMs are morphologically identical and express similar phenotypic markers in vivo, identifying injury responses specifically coordinated by microglia has historically been challenging. Here, we pharmacologically depleted microglia and use anatomical, histopathological, tract tracing, bulk and single cell RNA sequencing to reveal the cellular and molecular responses to SCI controlled by microglia. We show that microglia are vital for SCI recovery and coordinate injury responses in CNS-resident glia and infiltrating leukocytes. Depleting microglia exacerbates tissue damage and worsens functional recovery. Conversely, restoring select microglia-dependent signaling axes, identified through sequencing data, in microglia depleted mice prevents secondary damage and promotes recovery. Additional bioinformatics analyses reveal that optimal repair after SCI and likely other forms of neurological disease, might be achieved by co-opting key ligand-receptor interactions between microglia, astrocytes and MDMs.

2022-06-01 | GSE196928 | GEO

Infiltrating monocyte-derived macrophages polarizes in to anti-inflammatory and neuro-protective phenotype in a rat model of cerebral ischemia

Project description:To summarize our results, we found microglia and MDMs are functionally heterogeneous population contributing differently to the disease phenotype. Our data, suggest that during post-ischemic inflammation microglia exhibit pro-inflammatory phenotype, while infiltrating MDMs display anti-inflammatory and neuro-protective phenotype. Apart from up-regulation of some of the classical M2 marker in MDMs, our gene expression profiling using RNA-sequencing revealed a unique signature of MDMs with the up-regulation of genes associated with wound healing, MHCII antigen-presentation and tissue repair. Our results strongly suggest that MDMs infiltrating the CNS parenchyma during the sub-acute of post-ischemic inflammation might contribute to the endogenous mechanism of neuroprotection.

2018-12-31 | GSE86941 | GEO

Early Involvement of Peripherally Derived Monocytes in Inflammation in an NMO-Like Mouse Model [Monocytes]

Project description:Neuromyelitis optica (NMO) is an autoimmune inflammatory disease that primarily affects the spinal cord and optic nerves in the central nervous system (CNS). It is characterized by the presence of immunoglobulin G (IgG) antibodies against aquaporin 4, a protein found in astrocytes (known as NMO-IgG). Monocytes/macrophages and microglia accumulate at the active injury sites and contribute to the disease process. However, it is unclear whether these active cells originate from circulating monocytes/macrophages or resident microglia. Recent studies have investigated the role of microglia/macrophages in multiple sclerosis (MS) using specific microglial markers, such as P2ry12 and Tmem119, and have shown that active cells are derived from microglia. In contrast, the function of monocyte/macrophages and microglia in NMO has not been extensively studied. Therefore, this study aims to analyze the functions of monocytes/macrophages and microglia using microglial markers (P2ry12 and Tmem119) in an NMO-like mouse model and evaluate their role in the pathophysiology of NMO.

2024-01-17 | GSE235277 | GEO

Early Involvement of Peripherally Derived Monocytes in Inflammation in an NMO-Like Mouse Model [microglia]

2024-01-17 | GSE235276 | GEO

Peripherally derived macrophages can engraft the brain independent of irradiation and maintain an identity distinct from microglia

Project description:Peripherally derived macrophages infiltrate the brain after bone marrow transplantation and during central nervous system (CNS) inflammation. It was initially suggested that these engrafting cells were newly derived microglia and that irradiation was essential for engraftment to occur. However, it remains unclear whether brain-engrafting macrophages (beMφs) acquire a unique phenotype in the brain, whether long-term engraftment may occur without irradiation, and whether brain function is affected by the engrafted cells. In this study, we demonstrate that chronic, partial microglia depletion is sufficient for beMφs to populate the niche and that the presence of beMφs does not alter behavior. Furthermore, beMφs maintain a unique functional and transcriptional identity as compared with microglia. Overall, this study establishes beMφs as a unique CNS cell type and demonstrates that therapeutic engraftment of beMφs may be possible with irradiation-free conditioning regimens.

2018-04-07 | GSE84819 | GEO

Peripherally derived macrophages can engraft the brain independent of irradiation and maintain an identity distinct from microglia [LPS]

2018-04-07 | GSE108575 | GEO

Peripherally derived macrophages can engraft the brain independent of irradiation and maintain an identity distinct from microglia [GFP]

2018-04-07 | GSE108569 | GEO

Immune stimulation recruits a subset of pro-regenerative macrophages to the retina that promotes axonal regrowth of injured neurons

Project description:The multifaceted nature of neuroinflammation is highlighted by its ability to both aggravate and promote neuronal health. While in mammals retinal ganglion cells (RGCs) are unable to regenerate following injury, acute inflammation can induce axonal regrowth. However, the nature of the cells, cellular states and signalling pathways that drive this inflammation-induced regeneration have remained elusive. Here, we investigated the functional significance of macrophages during RGC de- and regeneration, by characterizing the inflammatory cascade evoked by optic nerve crush (ONC) injury, with or without local inflammatory stimulation in the vitreous. By combining single-cell RNA sequencing and fate mapping approaches, we elucidated the response of retinal microglia and recruited monocyte-derived macrophages (MDMs) to RGC injury. Importantly, inflammatory stimulation recruited large numbers of MDMs to the retina, which exhibited long-term engraftment and promoted axonal regrowth. Ligand-receptor analysis highlighted a subset of recruited macrophages that exhibited expression of pro-regenerative secreted factors, which were able to promote axon regrowth via paracrine signalling. Our work reveals how inflammation may promote CNS regeneration by modulating innate immune responses, providing a rationale for macrophage-centred strategies for driving neuronal repair following injury and disease.

2023-05-31 | GSE232470 | GEO

Transcriptional profiling of 5 days post LPC lesion after microglia ablation

Project description:Following all types of neurological injury, resident macrophages are activated locally, and blood-derived macrophages are recruited. Distinguishing the role of resident and blood-derived macrophages is complicated by the difficulty in distinguishing between these cell types because they mostly express the same molecular markers in a diseased state. To begin to understand the complexity of functions of resident and blood-derived macrophages following acute injury in the central nervous system (CNS) we ablated microglia, but not infiltrating macrophages, to determine their contribution following lysolecithin-induced demyelination .

2020-01-15 | GSE121484 | GEO

Genome-Wide Expression Profiling of human tumor-infiltrating microglia/macrophages

Project description:Microglia isolated from glioma patients gain anti-tumor activities upon poly (I:C) stimulation. Expression profiles of human tumor-infiltrating microglia/macrophages before (untreated) and after treatment with poly (I:C) for 48h (induced). Tumor-infiltrating microglia/macrophages were isolated from freshly excised brain tumors

2011-12-31 | E-GEOD-25289 | biostudies-arrayexpress

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