The myeloid cells of the central nervous system parenchyma

Ransohoff, Richard M.; Cardona, Astrid E.

doi:10.1038/nature09615

Cited by 676 publications

(607 citation statements)

References 104 publications

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“…Although many studies have found that microglia and monocytes/macrophages contribute to brain inflammation and injury in stroke, both cell types have overlapping functions and the ability to polarize toward pro-(M1) or antiinflammatory (M2) phenotypes. As such, their expression of common antigens and the morphological similarity between them have resulted in equivocal findings on their roles in stroke [9,[32][33][34]. The unique temporal and spatial presence of microglia and macrophages in the context of stroke suggest distinctive and complementary roles of each cell type in response to stroke injury.…”

Section: Impact Of Stroke On Immunitymentioning

confidence: 99%

Microglia and Monocyte-Derived Macrophages in Stroke

2016

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Historically, the brain has been considered an immune-privileged organ separated from the peripheral immune system by the blood-brain barrier. However, immune responses do occur in the brain in neurological conditions in which the integrity of the blood-brain barrier is compromised, exposing the brain to peripheral antigens and endogenous danger signals. While most of the associated pathological processes occur in the central nervous system, it is now clear that peripheral immune cells, especially mononuclear phagocytes, that infiltrate into the injury site play a key role in modulating the progression of primary brain injury development. As inflammation is a necessary and critical component for the subsequent injury resolution process, understanding the contribution of mononuclear phagocytes on the regulation of inflammatory responses may provide novel approaches for potential therapies. Furthermore, predisposed comorbid conditions at the time of stroke cause the alteration of stroke-induced immune and inflammatory responses and subsequently influence stroke outcome. In this review, we summarize a role for microglia and monocytes/macrophages in acute ischemic stroke in the context of normal and metabolically compromised conditions.

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Section: Impact Of Stroke On Immunitymentioning

confidence: 99%

Microglia and Monocyte-Derived Macrophages in Stroke

2016

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“…Under normal conditions, the microglia extend and retract their thin, highly ramified cell processes to continuously monitor the immediate microenvironment. 84 The processes of each microglial cell do not overlap; each cell surveys its own territory 85 ; and some cells, the juxtavascular microglia, directly contact the basal lamina of blood vessels. 86 On injury to the brain, including infection, inflammation, and trauma, microglial cells undergo a transformation from a resting to an activated state, assuming an ameboid shape and migrating to the site of injury to phagocytose dead cells, clear extracellular debris, and produce cytokines.…”

Section: Profile Of Virus Attachment In the Brainmentioning

confidence: 99%

Human Polyomavirus Receptor Distribution in Brain Parenchyma Contrasts with Receptor Distribution in Kidney and Choroid Plexus

Haley

O’Hara

Nelson

et al. 2015

The American Journal of Pathology

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The human polyomavirus, JCPyV, is the causative agent of progressive multifocal leukoencephalopathy, a rare demyelinating disease that occurs in the setting of prolonged immunosuppression. After initial asymptomatic infection, the virus establishes lifelong persistence in the kidney and possibly other extraneural sites. In rare instances, the virus traffics to the central nervous system, where oligodendrocytes, astrocytes, and glial precursors are susceptible to lytic infection, resulting in progressive multifocal leukoencephalopathy. The mechanisms by which the virus traffics to the central nervous system from peripheral sites remain unknown. Lactoseries tetrasaccharide c (LSTc), a pentasaccharide containing a terminal a2,6elinked sialic acid, is the major attachment receptor for polyomavirus. In addition to LSTc, type 2 serotonin receptors are required for facilitating virus entry into susceptible cells. We studied the distribution of virus receptors in kidney and brain using lectins, antibodies, and labeled virus. The distribution of LSTc, serotonin receptors, and virus binding sites overlapped in kidney and in the choroid plexus. In brain parenchyma, serotonin receptors were expressed on oligodendrocytes and astrocytes, but these cells were negative for LSTc and did not bind virus. LSTc was instead found on microglia and vascular endothelium, to which virus bound abundantly. Receptor distribution was not changed in the brains of patients with progressive multifocal leukoencephalopathy. Virus infection of oligodendrocytes and astrocytes during disease progression is LSTc independent. (Am J Pathol 2015, 185: 2246e2258; http://dx.doi.org/10.1016/j.ajpath.2015.04.003)The human polyomavirus (JCPyV) is the causative agent of progressive multifocal leukoencephalopathy (PML), a rapidly progressing, often fatal neurodegenerative disease. Although PML is rare, JCPyV infection is widespread, infecting approximately 50% to 80% of the healthy adult population. 1,2 As the initial infection is asymptomatic, the mode of JCPyV transmission is unknown. The virus establishes a persistent infection in the kidney and urinary tract of immunocompetent hosts, 3 and about 20% of these infected individuals shed virus in their urine. 4 JCPyV DNA has also been detected in other tissues, including B lymphocytes in the bone marrow, tonsillar stromal cells, lungs, spleen, and brain, 5e13 suggesting additional sites of viral persistence. The route of viral transmission from the initial site(s) of infection and latency to the central nervous system (CNS), the main site of pathogenesis, is not clearly understood.Under conditions of immunosuppression, JCPyV infects and destroys the myelin-producing oligodendrocytes, resulting in demyelination, which is the hallmark of this fatal disease; to a Supported by NIH grants R01NS043097 (W.J.A.) and P01NS065719 (W.J.A.).

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“…They actively move their branched processes to sense pathological alterations or disturbances to ultimately maintain CNS homeostasis [1][2][3][4]. Once abnormalities are detected, microglia dramatically transform into a reactive phenotype through a progressive series of cellular and molecular changes, including morphological hypertrophy, proliferation, and the expression of various genes [3,5].…”

Section: Introductionmentioning

confidence: 99%

IRF8 is a transcriptional determinant for microglial motility

Masuda

Nishimoto

Tomiyama

et al. 2014

Purinergic Signalling

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Microglia, the resident immune cells of the central nervous system, are constitutively mobile cells that undergo rapid directional movement toward sites of tissue disruption. However, transcriptional regulatory mechanisms of microglial motility remain unknown. In the present study, we show that interferon regulatory factor-8 (IRF8) regulates microglial motility. We found that ATP and complement component, C5a, induced chemotaxis of IRF8 wild-type microglia. However, these responses were markedly suppressed in microglia lacking IRF8 (Irf8 −/− ). In a consistent manner, phosphorylation of Akt (which plays a crucial role in ATP-induced chemotaxis) was abolished in Irf8 −/− microglia. Real-time polymerase chain reaction analysis revealed that motility-related microglial genes such as P2Y 12 receptor were significantly suppressed in Irf8 −/− microglia. Furthermore, Irf8 −/− microglia exhibited a differential expression pattern of nucleotidedegrading enzymes compared with their wild-type counterparts. Overall, our findings suggest that IRF8 may regulate microglial motility via the control of microglial gene expression.

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The myeloid cells of the central nervous system parenchyma

Cited by 676 publications

References 104 publications

Microglia and Monocyte-Derived Macrophages in Stroke

Microglia and Monocyte-Derived Macrophages in Stroke

Human Polyomavirus Receptor Distribution in Brain Parenchyma Contrasts with Receptor Distribution in Kidney and Choroid Plexus

IRF8 is a transcriptional determinant for microglial motility

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