title: Phenotypic changes in the brain of SIV-infected macaques exposed to methamphetamine parallel macrophage activation patterns induced by the common gamma-chain cytokine system.
abstract: One factor in the development of neuroAIDS is the increase in the migration of pro-inflammatory CD8 T cells across the blood-brain barrier. Typically these cells are involved with keeping the viral load down. However, the persistence of above average numbers of CD8 T cells in the brain, not necessarily specific to viral peptides, is facilitated by the upregulation of IL15 from astrocytes, in the absence of IL2, in the brain environment. Both IL15 and IL2 are common gamma chain (γc) cytokines. Here, using the non-human primate model of neuroAIDS, we have demonstrated that exposure to methamphetamine, a powerful illicit drug that has been associated with HIV exposure and neuroAIDS severity, can cause an increase in molecules of the γc system. Among these molecules, IL15, which is upregulated in astrocytes by methamphetamine, and that induces the proliferation of T cells, may also be involved in driving an inflammatory phenotype in innate immune cells of the brain. Therefore, methamphetamine and IL15 may be critical in the development and aggravation of central nervous system immune-mediated inflammatory pathology in HIV-infected drug abusers.
authors.affiliation: Department of Molecular and Cellular Neurosciences, The Scripps Research Institute La Jolla, CA, USA.
authors.forename: Nikki
authors.initials: N
authors.lastname: Bortell
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center Omaha, NE, USA.
authors.forename: Brenda
authors.initials: B
authors.lastname: Morsey
authors.affiliation: Department of Molecular and Cellular Neurosciences, The Scripps Research Institute La Jolla, CA, USA.
authors.forename: Liana
authors.initials: L
authors.lastname: Basova
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center Omaha, NE, USA.
authors.forename: Howard S
authors.initials: HS
authors.lastname: Fox
authors.affiliation: Department of Molecular and Cellular Neurosciences, The Scripps Research Institute La Jolla, CA, USA.
authors.forename: Maria Cecilia Garibaldi
authors.initials: MC
authors.lastname: Marcondes
keywords: HIV infections; IL15; NeuroAIDS; SIV; gamma-chain cytokines; macrophages; methamphetamine; microglia