CCR2 on Peripheral Blood CD14 + CD16 + Monocytes Correlates with Neuronal Damage, HIV-Associated Neurocognitive Disorders, and Peripheral HIV DNA: reseeding of CNS reservoirs?

Mike Veenstra, Desiree A. Byrd, Matilde Inglese, Korhan Buyukturkoglu, Dionna W. Williams, Lazar Fleysher, Ming Li, Lucio Gama, Rosiris León-Rivera, Tina M. Calderon, Janice E. Clements, Susan Morgello, Joan W. Berman

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

HIV-associated neurocognitive disorders (HAND) occur in ~50% of HIV infected individuals despite combined antiretroviral therapy. Transmigration into the CNS of CD14 + CD16 + 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 CD14 + CD16 + monocytes serves as a potential peripheral blood biomarker of HAND, we examined a cohort of 45 HIV infected people. We correlated CCR2 on CD14 + CD16 + monocytes with cognitive status, proton magnetic resonance spectroscopy ( 1 H-MRS) measured neurometabolite levels, and peripheral blood mononuclear cell (PBMC) HIV DNA copies. We determined that CCR2 was increased specifically on CD14 + CD16 + 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 CD14 + CD16 + monocytes with total N-Acetyl Aspartate (tNAA)/total Creatine (tCr) (r 2 = 0.348, p = 0.01) and Glutamine-Glutamate (Glx)/tCr (r 2 = 0.356, p = 0.01) in the right and left caudate nucleus, respectively. CCR2 on CD14 + CD16 + 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 CD14 + CD16 + monocytes may be a peripheral blood biomarker of HAND, indicative of increased HIV infected CD14 + CD16 + monocyte entry into the CNS that possibly increases the macrophage viral reservoir and contributes to HAND.

Original languageEnglish (US)
Pages (from-to)120-133
Number of pages14
JournalJournal of Neuroimmune Pharmacology
Volume14
Issue number1
DOIs
StatePublished - Mar 15 2019

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Keywords

  • CCR2
  • CD14 CD16 Monocytes
  • HAND
  • HIV
  • MRI/MRS
  • ddPCR

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Immunology and Allergy
  • Immunology
  • Pharmacology

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