title: When human immunodeficiency virus meets chemokines and microglia: neuroprotection or neurodegeneration?
abstract: Chemokines are chemotactic cytokines that were originally discovered as promoters of leukocyte proliferation and mobility. In recent years, however, evidence has demonstrated constitutive expression of chemokines and chemokine receptors in a variety of cells in the central and peripheral nervous system and has proposed a role for chemokines in neurodegenerative diseases characterized by inflammation and microglia proliferation. In addition, chemokine receptors, and in particular CXCR4 and CCR5, mediate human immunodeficiency virus type 1 (HIV) infection of immunocompetent cells as well as microglia. Subsequently, HIV, through a variety of mechanisms, promotes synapto-dendritic alterations and neuronal loss that ultimately lead to motor and cognitive impairments. These events are accompanied by microglia activation. Nevertheless, a microglia-mediated mechanism of neuronal degeneration alone cannot fully explain some of the pathological features of HIV infected brain such as synaptic simplification. In this article, we present evidence that some of the microglia responses to HIV are beneficial and neuroprotective. These include the ability of microglia to release anti-inflammatory cytokines, to remove dying cells and to promote axonal sprouting.
authors.affiliation: Department of Neuroscience, Georgetown University Medical Center, Research Building, Room EP04 Box 571464, Washington, DC 20057, USA. moccheti@georgetown.edu
authors.forename: Italo
authors.initials: I
authors.lastname: Mocchetti
authors.forename: Lee A
authors.initials: LA
authors.lastname: Campbell
authors.forename: G Jean
authors.initials: GJ
authors.lastname: Harry
authors.forename: Valeriya
authors.initials: V
authors.lastname: Avdoshina
mesh_terms: D015526:AIDS Dementia Complex / Q000473:pathology; D000818:Animals; D018925:Chemokines / Q000502:physiology*; D006678:HIV / Q000276:immunology*; D015658:HIV Infections / Q000473:pathology; D006801:Humans; D008262:Macrophage Activation / Q000502:physiology; D017628:Microglia / Q000276:immunology*; D019636:Neurodegenerative Diseases / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D019713:Receptors, CCR5 / Q000187:drug effects / Q000502:physiology; D019718:Receptors, CXCR4 / Q000187:drug effects / Q000502:physiology; D014764:Viral Proteins / Q000502:physiology
chemical_list: D018925:Chemokines; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D014764:Viral Proteins