CCR2 on Peripheral Blood CD14CD16 Monocytes Correlates with Neuronal Damage, HIV-Associated Neurocognitive Disorders, and Peripheral HIV DNA: reseeding of CNS reservoirs?

TitleCCR2 on Peripheral Blood CD14CD16 Monocytes Correlates with Neuronal Damage, HIV-Associated Neurocognitive Disorders, and Peripheral HIV DNA: reseeding of CNS reservoirs?
Publication TypeJournal Article
Year of Publication2019
AuthorsVeenstra, M, Byrd, DA, Inglese, M, Buyukturkoglu, K, Williams, DW, Fleysher, L, Li, M, Gama, L, Leon-Rivera, R, Calderon, TM, Clements, JE, Morgello, S, Berman, JW
JournalJ Neuroimmune Pharmacol
Volume14
Issue1
Pagination120-133
Date Published2019 03
ISSN1557-1904
KeywordsAdult, Aged, AIDS Dementia Complex, Biomarkers, DNA, Viral, Female, GPI-Linked Proteins, Humans, Lipopolysaccharide Receptors, Male, Middle Aged, Monocytes, Receptors, CCR2, Receptors, IgG
Abstract

HIV-associated neurocognitive disorders (HAND) occur in ~50% of HIV infected individuals despite combined antiretroviral therapy. Transmigration into the CNS of CD14CD16 monocytes, particularly those that are HIV infected and express increased surface chemokine receptor CCR2, contributes to neuroinflammation and HAND. To examine whether in HIV infected individuals CCR2 on CD14CD16 monocytes serves as a potential peripheral blood biomarker of HAND, we examined a cohort of 45 HIV infected people. We correlated CCR2 on CD14CD16 monocytes with cognitive status, proton magnetic resonance spectroscopy (H-MRS) measured neurometabolite levels, and peripheral blood mononuclear cell (PBMC) HIV DNA copies. We determined that CCR2 was increased specifically on CD14CD16 monocytes from people with HAND (median [interquartile range (IQR)]) (63.3 [51.6, 79.0]), compared to those who were not cognitively impaired (38.8 [26.7, 56.4]) or those with neuropsychological impairment due to causes other than HIV (39.8 [30.2, 46.5]). CCR2 was associated with neuronal damage, based on the inverse correlation of CCR2 on CD14CD16 monocytes with total N-Acetyl Aspartate (tNAA)/total Creatine (tCr) (r = 0.348, p = 0.01) and Glutamine-Glutamate (Glx)/tCr (r = 0.356, p = 0.01) in the right and left caudate nucleus, respectively. CCR2 on CD14CD16 monocytes also correlated with PBMC HIV DNA copies (ρ = 0.618, p = 0.02) that has previously been associated with HAND. These findings suggest that CCR2 on CD14CD16 monocytes may be a peripheral blood biomarker of HAND, indicative of increased HIV infected CD14CD16 monocyte entry into the CNS that possibly increases the macrophage viral reservoir and contributes to HAND.

DOI10.1007/s11481-018-9792-7
Alternate JournalJ Neuroimmune Pharmacol
PubMed ID29981000
PubMed Central IDPMC6320730
Grant ListTL1 TR001072 / TR / NCATS NIH HHS / United States
U24 MH100931 / MH / NIMH NIH HHS / United States
R25 MH080663 / MH / NIMH NIH HHS / United States
R01 MH112391 / MH / NIMH NIH HHS / United States
R01 AI127142 / AI / NIAID NIH HHS / United States
R21 MH102113 / MH / NIMH NIH HHS / United States
R01 NS077869 / NS / NINDS NIH HHS / United States
P30 AI124414 / AI / NIAID NIH HHS / United States
R01 MH090958 / MH / NIMH NIH HHS / United States
UL1 TR002556 / TR / NCATS NIH HHS / United States
R01 MH075679 / MH / NIMH NIH HHS / United States
T32 GM007288 / GM / NIGMS NIH HHS / United States