title: Impairment of blood-cerebrospinal fluid barrier properties by retrovirus-activated T lymphocytes: reduction in cerebrospinal fluid-to-blood efflux of prostaglandin E2.
abstract: The choroid plexus epithelium forms the interface between the blood and the CSF. In conjunction with the tight junctions restricting the paracellular pathway, polarized specific transport systems in the choroidal epithelium allow a fine regulation of CSF-borne biologically active mediators. The highly vascularized stroma delimited by the choroidal epithelium can be a reservoir for retrovirus-infected or activated immune cells. In this work, new insight in the implication of the blood-CSF barrier in neuroinfectious and inflammatory diseases is provided by using a differentiated cellular model of the choroidal epithelium, exposed to infected T lymphocytes. We demonstrate that T cells activated by a retroviral infection, but not non-infected cells, reduce the transporter-mediated CSF-to-blood efflux of organic anions, in particular that of the potent pro-inflammatory prostaglandin PGE2, via the release of soluble factors. A moderate alteration of the paracellular permeability also occurs. We identified the viral protein Tax, oxygenated free radicals, matrix-metalloproteinases and pro-inflammatory cytokines as active molecules released during the exposure of the epithelium to infected T cells. Among them, tumour necrosis factor and interleukin 1 are directly involved in the mechanism underlying the decrease in some choroidal organic anion efflux. Given the strong involvement of CSF-borne PGE2 in sickness behaviour syndrome, these data suggest that the blood-CSF barrier plays an important role in the pathophysiology of neuroinflammation and neuroinfection, via changes in the transport processes controlling the CSF biodisposition of PGE2.
authors: INSERM U433, Université Claude Bernard Lyon 1, Faculté de Médecine RTH Laennec, Lyon, France.
authors: Seng Thuon
authors: ST
authors: Khuth
authors: Nathalie
authors: N
authors: Strazielle
authors: Pascale
authors: P
authors: Giraudon
authors: Marie-Françoise
authors: MF
authors: Belin
authors: Jean-François
authors: JF
authors: Ghersi-Egea
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001812:Blood-Brain Barrier / Q000276:immunology* / Q000821:virology; D002450:Cell Communication / Q000276:immunology; D002478:Cells, Cultured; D020805:Central Nervous System Viral Diseases / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D002555:Cerebrospinal Fluid / Q000276:immunology / Q000378:metabolism; D002831:Choroid Plexus / Q000276:immunology* / Q000821:virology; D018920:Coculture Techniques; D015232:Dinoprostone / Q000378:metabolism*; D004660:Encephalitis / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D004847:Epithelial Cells / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D005609:Free Radicals / Q000276:immunology / Q000378:metabolism; D016356:Gene Products, tax / Q000276:immunology / Q000378:metabolism; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D020782:Matrix Metalloproteinases / Q000276:immunology / Q000378:metabolism; D051381:Rats; D012190:Retroviridae / Q000276:immunology; D012192:Retroviridae Infections / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology; D017201:Virus Shedding / Q000276:immunology
chemical_list: D005609:Free Radicals; D016356:Gene Products, tax; D018836:Inflammation Mediators; D020782:Matrix Metalloproteinases; D015232:Dinoprostone