Journal
JOURNAL OF NEUROIMMUNE PHARMACOLOGY
Volume 12, Issue 2, Pages 353-370Publisher
SPRINGER
DOI: 10.1007/s11481-017-9726-9
Keywords
CD14(+)CD16(+) monocytes; Substance abuse; Dopamine; CNS HIV reservoirs; Neuroinflammation; HAND
Categories
Funding
- U.S. NIH [DA025567, MH075679, MH090958, DA029476, MH096625, Al035004, Al142590, MH083501, MH100931]
- Mount Sinai Institute for NeuroAIDS Disparities Pilot Funds [MH080663]
- United Negro College Fund/Merck Graduate Science Dissertation Fellowship
- Center for AIDS Research at the Albert Einstein College of Medicine, Montefiore Medical Center [CFAR/AI051519]
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In human immunodeficiency virus-1 (HIV) infected individuals, substance abuse may accelerate the development and/or increase the severity of HIV associated neurocognitive disorders (HAND). It is proposed that CD14(+)CD16(+) monocytes mediate HIV entry into the central nervous system (CNS) and that uninfected and infected CD14(+)CD16(+) monocyte transmigration across the blood brain barrier (BBB) contributes to the establishment and propagation of CNS HIV viral reservoirs and chronic neuroinflammation, important factors in the development of HAND. The effects of substance abuse on the frequency of CD14(+)CD16(+) monocytes in the peripheral circulation and on the entry of these cells into the CNS during HIV neuropathogenesis are not known. PBMC from HIV infected individuals were analyzed by flow cytometry and we demonstrate that the frequency of peripheral blood CD14(+)CD16(+) monocytes in HIV infected substance abusers is increased when compared to those without active substance use. Since drug use elevates extracellular dopamine concentrations in the CNS, we examined the effects of dopamine on CD14(+)CD16(+) monocyte transmigration across our in vitro model of the human BBB. The transmigration of this monocyte subpopulation is increased by dopamine and the dopamine receptor agonist, SKF 38393, implicating D1-like dopamine receptors in the increase in transmigration elicited by this neurotransmitter. Thus, elevated extracellular CNS dopamine may be a novel common mechanism by which active substance use increases uninfected and HIV infected CD14(+)CD16(+) monocyte transmigration across the BBB. The influx of these cells into the CNS may increase viral seeding and neuroinflammation, contributing to the development of HIV associated neurocognitive impairments.
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