Microglial and Astrocyte Chemokines Regulate Monocyte Migration through the Blood-Brain Barrier in Human Immunodeficiency Virus-1 Encephalitis

Persidsky, Yuri; Ghorpade, Anuja; Rasmussen, Jennifer; Limoges, Jenae; Liu, Xiao Juan; Stins, Monique F.; Fiala, Milan; Way, Dennis; Kim, Kwang Sik; Witte, Marlys H.; Weinand, Martin E.; Carhart, Leeroy; Gendelman, Howard Eliot

doi:10.1016/s0002-9440(10)65476-4

Cited by 263 publications

(199 citation statements)

References 57 publications

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“…These cells are involved in regulating neuronal development, innate immune response, and wound healing, and can act as antigen-presenting cells in adaptive immunity (Streit et al 2005;Ajami et al 2007). In addition, different blood-borne immune cell populations, including neutrophils, T cells, and macrophages, can interact with CNS vessels when activated and are thought to regulate BBB properties in response to infection, injury, and disease by releasing reactive oxygen species that can increase vascular permeability (Persidsky et al 1999;Hudson et al 2005). Identifying the mechanisms by which both the immune cells and the BBB become "activated" to interact may be important in deciphering the mechanisms by which the BBB is disrupted during different neurological diseases.…”

Section: Basement Membranementioning

confidence: 99%

The Blood–Brain Barrier

Daneman

Prat

2015

Cold Spring Harb Perspect Biol

2,248

1,640

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Blood vessels are critical to deliver oxygen and nutrients to all of the tissues and organs throughout the body. The blood vessels that vascularize the central nervous system (CNS) possess unique properties, termed the blood-brain barrier, which allow these vessels to tightly regulate the movement of ions, molecules, and cells between the blood and the brain. This precise control of CNS homeostasis allows for proper neuronal function and also protects the neural tissue from toxins and pathogens, and alterations of these barrier properties are an important component of pathology and progression of different neurological diseases. The physiological barrier is coordinated by a series of physical, transport, and metabolic properties possessed by the endothelial cells (ECs) that form the walls of the blood vessels, and these properties are regulated by interactions with different vascular, immune, and neural cells. Understanding how these different cell populations interact to regulate the barrier properties is essential for understanding how the brain functions during health and disease.

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Section: Basement Membranementioning

confidence: 99%

The Blood–Brain Barrier

Daneman

Prat

2015

Cold Spring Harb Perspect Biol

2,248

1,640

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“…64,65 Some pathological conditions such as viral or bacterial infection can disrupt the integrity of the BBB and allow less restricted passage of leukocytes from the systemic circulation into the brain and additional monocytes to enter the brain. 66,67 During the course of HIV infection, monocytes cross in response to proinflammatory cytokines released by astrocytes and parenchymal myeloid cells. 68,69 After HIV neuroinvasion, the BBB is disrupted as a result of loss of transmembrane tight junction integrity in the neuroendothelium, 70 and glycoprotein 120 has been shown to contribute to BBB leakiness, perhaps by increased expression of proteases.…”

Section: Direct Binding Of Jcpyv To Barriers Of the Cnsmentioning

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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“…3b). As Cop-1 may induce expression of growth factors by DC and, thus, indirectly provide neuroprotection, we performed [34,35]. DC labeled with the fluorescence marker Calcein-AM, were placed in the upper chamber of BBB constructs containing primary human brain microvascular endothelial monolayers.…”

Section: Direct Cop-1-induced Neuroprotectionmentioning

confidence: 99%

T cell independent mechanism for copolymer‐1‐induced neuroprotection

et al. 2007

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Despite active investigation of copolymer-1 (Cop-1) for nearly 40 years the mechanisms underlying its neuroprotective properties remain contentious. Nonetheless, current dogma for Cop-1 neuroprotective activities in autoimmune and neurodegenerative diseases include bystander suppression of autoimmune T cells and attenuation of microglial responses. In this report, we demonstrate that Cop-1 interacts directly with primary human neurons and decreases neuronal cell death induced by staurosporine or oxidative stress. This neuroprotection is mediated through protein kinase Ca and brainderived neurotrophic factor. Dendritic cells (DC) uptake Cop-1, deliver it to the injury site, and release it in an active form. Interactions between Cop-1 and DC enhance DC blood brain barrier migration. In a rat model with optic nerve crush injury, Cop-1-primed DC induce T cell independent neuroprotection. These findings may facilitate the development of neuroprotective approaches using DC-mediated Cop-1 delivery to diseased nervous tissue. IntroductionCopolymer-1 (Cop-1) was developed to mimic the encephalitogenic epitope of myelin basic protein (MBP). However, when administered in complete Freund's adjuvant it failed to induce experimental autoimmune encephalitis (EAE). Surprisingly, Cop-1 suppressed EAE when administered with MBP [1][2][3][4]. These observations led to the development of Cop-1 as a treatment for relapsing-remitting multiple sclerosis [5][6][7][8]. Over the past three decades, scientists have tried to determine how Cop-1 exerts its therapeutic effects [2,4,9,10]. Cop-1-specific T cells partially cross-react with MBP, leading to the secretion of neurotrophic and antiinflammatory factors such as brain derived neurotrophic factor (BDNF), glial cell-derived neurotrophic factor, [11][12][13]. [17], and experimentally induced encephalitis [18]. The mechanism(s) underlying Cop-1-induced neuroprotection were attributed to T cells. T cells modulate microglial and astrocyte responses and as such attenuate toxic inflammatory activities and neurodegeneration [11,12,19]. Indeed, the mechanism underlying T cellinduced neuroprotection is linked to modulation of microglial function [20] and increased production of neurotrophins at the site of injury [11,12]. After central nervous system (CNS) injury microglia commonly display a neurotoxic phenotype with local production of glutamate and increased expression of nitric oxide synthase (iNOS), pro-inflammatory cytokines, quinolinic acid and arachidonic acid and its metabolites [21,22]. T cells can induce a neuroprotective microglial phenotype [20].Under certain conditions with progressive neurodegeneration the Cop-1 neuroprotective response is seen before an adaptive immune response is generated [15,17,23], suggesting that Cop-1 induced neuroprotection may be, at least in part, T cell independent. We now demonstrate that Cop-1 treatment of primary human neurons intoxicated with staurosporine or reactiveoxygen species significantly decreases cell death. This neuroprotection is associ...

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Microglial and Astrocyte Chemokines Regulate Monocyte Migration through the Blood-Brain Barrier in Human Immunodeficiency Virus-1 Encephalitis

Cited by 263 publications

References 57 publications

The Blood–Brain Barrier

The Blood–Brain Barrier

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

T cell independent mechanism for copolymer‐1‐induced neuroprotection

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