title: Monocytes mediate HIV neuropathogenesis: mechanisms that contribute to HIV associated neurocognitive disorders.
abstract: HIV infected people are living longer due to the success of combined antiretroviral therapy (cART). However, greater than 40-70% of HIV infected individuals develop HIV associated neurocognitive disorders (HAND) that continues to be a major public health issue. While cART reduces peripheral virus, it does not limit the low level, chronic neuroinflammation that is ongoing during the neuropathogenesis of HIV. Monocyte transmigration across the blood brain barrier (BBB), specifically that of the mature CD14(+)CD16(+) population that is highly susceptible to HIV infection, is critical to the establishment of HAND as these cells bring virus into the brain and mediate the neuroinflammation that persists, even if at low levels, despite antiretroviral therapy. CD14(+)CD16(+) monocytes preferentially migrate into the CNS early during peripheral HIV infection in response to chemotactic signals, including those from CCL2 and CXCL12. Once within the brain, monocytes differentiate into macrophages and elaborate inflammatory mediators. Monocytes/macrophages constitute a viral reservoir within the CNS and these latently infected cells may perpetuate the neuropathogenesis of HIV. This review will discuss mechanisms that mediate transmigration of CD14(+)CD16(+) monocytes across the BBB in the context of HIV infection, the contribution of these cells to the neuropathogenesis of HIV, and potential monocyte/macrophage biomarkers to identify HAND and monitor its progression.
authors.forename: Dionna W
authors.initials: DW
authors.lastname: Williams
authors.forename: Mike
authors.initials: M
authors.lastname: Veenstra
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Gaskill
authors.forename: Susan
authors.initials: S
authors.lastname: Morgello
authors.forename: Tina M
authors.initials: TM
authors.lastname: Calderon
authors.affiliation: Department of Pathology, F727, Albert Einstein College of Medicine, 1300 Morris Park Ave. Bronx, NY, 10461, USA. joan.berman@einstein.yu.edu.
authors.forename: Joan W
authors.initials: JW
authors.lastname: Berman
mesh_terms: D015658:HIV Infections / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism*; D017452:Receptors, IgG / Q000378:metabolism
chemical_list: D018950:Lipopolysaccharide Receptors; D017452:Receptors, IgG