Effect of morphine and SIV on dendritic cell trafficking into the central nervous system of rhesus macaques.
Recruitment of immune cells such as monocytes/macrophages and dendritic cells (DCs) across the blood-brain barrier (BBB) has been documented in diseases involving neuroinflammation. Neuroinvasion by HIV leads to neurocognitive diseases and alters the permeability of the BBB. Likewise, many HIV patients use drugs of abuse such as morphine, which can further compromise the BBB. While the role of monocytes and macrophages in neuroAIDS is well established, research demonstrating the presence and role of DCs in the CNS during HIV infection has not been developed yet. In this respect, this study explored the presence of DCs in the brain parenchyma of rhesus macaques infected with a neurovirulent form of SIV (SIV mac239 R71/17E) and administered with morphine. Cells positive for DC markers including CD11c (integrin), macDC-SIGN (dendritic cell-specific ICAM-3 grabbing nonintegrin), CD83 (a maturation factor), and HLA-DR (MHC class II) were consistently found in the brain parenchyma of SIV-infected macaques as well as infected macaques on morphine. Control animals did not exhibit any DC presence in their brains. These results provide first evidence of DCs' relevance in NeuroAIDS vis-à-vis drugs of abuse and open new avenues of understanding and investigative HIV-CNS inflictions.
Department of Microbiology and Immunology, and the Drexel Institute for Biotechnology and Virology Research, Drexel University College of Medicine, 3805 Old Easton Road, Doylestown, PA, 18902, USA.
Rebecca
R
Hollenbach
Divya
D
Sagar
Zafar K
ZK
Khan
Shannon
S
Callen
Honghong
H
Yao
Jasmine
J
Shirazi
Shilpa
S
Buch
Pooja
P
Jain
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D015415:Biomarkers / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000276:immunology / Q000473:pathology / Q000821:virology; D001921:Brain / Q000187:drug effects* / Q000276:immunology / Q000473:pathology / Q000821:virology; D002465:Cell Movement / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000473:pathology / Q000821:virology; D015870:Gene Expression; D008253:Macaca mulatta; D009020:Morphine / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000276:immunology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000473:pathology* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000502:physiology
D015703:Antigens, CD; D015415:Biomarkers; D009294:Narcotics; D009419:Nerve Tissue Proteins; D009020:Morphine