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 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

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 (1H-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) (r2 = 0.348, p = 0.01) and Glutamine-Glutamate (Glx)/tCr (r2 = 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)1-14
Number of pages14
JournalJournal of NeuroImmune Pharmacology
DOIs
StateAccepted/In press - Jul 6 2018

Fingerprint

Monocytes
HIV
DNA
Creatine
Neurocognitive Disorders
Blood Cells
Biomarkers
Caudate Nucleus
Chemokine Receptors
Glutamine
Glutamic Acid
Macrophages

Keywords

  • CCR2
  • CD14CD16 Monocytes
  • ddPCR
  • HAND
  • HIV
  • MRI/MRS

ASJC Scopus subject areas

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

Cite this

CCR2 on Peripheral Blood CD14+CD16+ Monocytes Correlates with Neuronal Damage, HIV-Associated Neurocognitive Disorders, and Peripheral HIV DNA : reseeding of CNS reservoirs? / Veenstra, Mike; Byrd, Desiree A.; Inglese, Matilde; Buyukturkoglu, Korhan; Williams, Dionna; Fleysher, Lazar; Li, Ming; Gama, Lucio; León-Rivera, Rosiris; Calderon, Tina M.; Clements, Janice E; Morgello, Susan; Berman, Joan W.

In: Journal of NeuroImmune Pharmacology, 06.07.2018, p. 1-14.

Research output: Contribution to journalArticle

Veenstra, Mike ; Byrd, Desiree A. ; Inglese, Matilde ; Buyukturkoglu, Korhan ; Williams, Dionna ; Fleysher, Lazar ; Li, Ming ; Gama, Lucio ; León-Rivera, Rosiris ; Calderon, Tina M. ; Clements, Janice E ; Morgello, Susan ; Berman, Joan W. / CCR2 on Peripheral Blood CD14+CD16+ Monocytes Correlates with Neuronal Damage, HIV-Associated Neurocognitive Disorders, and Peripheral HIV DNA : reseeding of CNS reservoirs?. In: Journal of NeuroImmune Pharmacology. 2018 ; pp. 1-14.
@article{c6fdd23240184ab79e566629a252bd87,
title = "CCR2 on Peripheral Blood CD14+CD16+ Monocytes Correlates with Neuronal Damage, HIV-Associated Neurocognitive Disorders, and Peripheral HIV DNA: reseeding of CNS reservoirs?",
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 (1H-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) (r2 = 0.348, p = 0.01) and Glutamine-Glutamate (Glx)/tCr (r2 = 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.",
keywords = "CCR2, CD14CD16 Monocytes, ddPCR, HAND, HIV, MRI/MRS",
author = "Mike Veenstra and Byrd, {Desiree A.} and Matilde Inglese and Korhan Buyukturkoglu and Dionna Williams and Lazar Fleysher and Ming Li and Lucio Gama and Rosiris Le{\'o}n-Rivera and Calderon, {Tina M.} and Clements, {Janice E} and Susan Morgello and Berman, {Joan W.}",
year = "2018",
month = "7",
day = "6",
doi = "10.1007/s11481-018-9792-7",
language = "English (US)",
pages = "1--14",
journal = "Journal of NeuroImmune Pharmacology",
issn = "1557-1890",
publisher = "Springer New York",

}

TY - JOUR

T1 - CCR2 on Peripheral Blood CD14+CD16+ Monocytes Correlates with Neuronal Damage, HIV-Associated Neurocognitive Disorders, and Peripheral HIV DNA

T2 - reseeding of CNS reservoirs?

AU - Veenstra, Mike

AU - Byrd, Desiree A.

AU - Inglese, Matilde

AU - Buyukturkoglu, Korhan

AU - Williams, Dionna

AU - Fleysher, Lazar

AU - Li, Ming

AU - Gama, Lucio

AU - León-Rivera, Rosiris

AU - Calderon, Tina M.

AU - Clements, Janice E

AU - Morgello, Susan

AU - Berman, Joan W.

PY - 2018/7/6

Y1 - 2018/7/6

N2 - 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 (1H-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) (r2 = 0.348, p = 0.01) and Glutamine-Glutamate (Glx)/tCr (r2 = 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.

AB - 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 (1H-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) (r2 = 0.348, p = 0.01) and Glutamine-Glutamate (Glx)/tCr (r2 = 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.

KW - CCR2

KW - CD14CD16 Monocytes

KW - ddPCR

KW - HAND

KW - HIV

KW - MRI/MRS

UR - http://www.scopus.com/inward/record.url?scp=85049574820&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85049574820&partnerID=8YFLogxK

U2 - 10.1007/s11481-018-9792-7

DO - 10.1007/s11481-018-9792-7

M3 - Article

C2 - 29981000

AN - SCOPUS:85049574820

SP - 1

EP - 14

JO - Journal of NeuroImmune Pharmacology

JF - Journal of NeuroImmune Pharmacology

SN - 1557-1890

ER -