Alterations in Th17 Cells and Non-Classical Monocytes as a Signature of Subclinical Coronary Artery Atherosclerosis during ART-Treated HIV-1 Infection

Cardiovascular disease (CVD) remains an important comorbidity in people living with HIV-1 (PLWH) receiving antiretroviral therapy (ART). Our previous studies performed in the Canadian HIV/Aging Cohort Study (CHACS) (>40 years-old; Framingham Risk Score (FRS) > 5%) revealed a 2–3-fold increase...

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Main Authors: Tomas Raul Wiche Salinas, Yuwei Zhang, Annie Gosselin, Natalia Fonseca Rosario, Mohamed El-Far, Ali Filali-Mouhim, Jean-Pierre Routy, Carl Chartrand-Lefebvre, Alan L. Landay, Madeleine Durand, Cécile L. Tremblay, Petronela Ancuta
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Language:English
Published: MDPI AG 2024-01-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/13/2/157
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author Tomas Raul Wiche Salinas
Yuwei Zhang
Annie Gosselin
Natalia Fonseca Rosario
Mohamed El-Far
Ali Filali-Mouhim
Jean-Pierre Routy
Carl Chartrand-Lefebvre
Alan L. Landay
Madeleine Durand
Cécile L. Tremblay
Petronela Ancuta
author_facet Tomas Raul Wiche Salinas
Yuwei Zhang
Annie Gosselin
Natalia Fonseca Rosario
Mohamed El-Far
Ali Filali-Mouhim
Jean-Pierre Routy
Carl Chartrand-Lefebvre
Alan L. Landay
Madeleine Durand
Cécile L. Tremblay
Petronela Ancuta
author_sort Tomas Raul Wiche Salinas
collection DOAJ
description Cardiovascular disease (CVD) remains an important comorbidity in people living with HIV-1 (PLWH) receiving antiretroviral therapy (ART). Our previous studies performed in the Canadian HIV/Aging Cohort Study (CHACS) (>40 years-old; Framingham Risk Score (FRS) > 5%) revealed a 2–3-fold increase in non-calcified coronary artery atherosclerosis (CAA) plaque burden, measured by computed tomography angiography scan (CTAScan) as the total (TPV) and low attenuated plaque volume (LAPV), in ART-treated PLWH (HIV+) versus uninfected controls (HIV−). In an effort to identify novel correlates of subclinical CAA, markers of intestinal damage (sCD14, LBP, FABP2); cell trafficking/inflammation (CCL20, CX3CL1, MIF, CCL25); subsets of Th17-polarized and regulatory (Tregs) CD4<sup>+</sup> T-cells, classical/intermediate/non-classical monocytes, and myeloid/plasmacytoid dendritic cells were studied in relationship with HIV and TPV/LAPV status. The TPV detection/values coincided with higher plasma sCD14, FABP2, CCL20, MIF, CX3CL1, and triglyceride levels; lower Th17/Treg ratios; and classical monocyte expansion. Among HIV<sup>+</sup>, TPV<sup>+</sup> versus TPV<sup>−</sup> exhibited lower Th17 frequencies, reduced Th17/Treg ratios, higher frequencies of non-classical CCR9<sup>low</sup>HLADR<sup>high</sup> monocytes, and increased plasma fibrinogen levels. Finally, Th17/Treg ratios and non-classical CCR9<sup>low</sup>HLADR<sup>high</sup> monocyte frequencies remained associated with TPV/LAPV after adjusting for FRS and HIV/ART duration in a logistic regression model. These findings point to Th17 paucity and non-classical monocyte abundance as novel immunological correlates of subclinical CAA that may fuel the CVD risk in ART-treated PLWH.
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spelling doaj.art-6e3d5b0e9ac945fea97b1abf8a1ce9302024-01-29T13:50:26ZengMDPI AGCells2073-44092024-01-0113215710.3390/cells13020157Alterations in Th17 Cells and Non-Classical Monocytes as a Signature of Subclinical Coronary Artery Atherosclerosis during ART-Treated HIV-1 InfectionTomas Raul Wiche Salinas0Yuwei Zhang1Annie Gosselin2Natalia Fonseca Rosario3Mohamed El-Far4Ali Filali-Mouhim5Jean-Pierre Routy6Carl Chartrand-Lefebvre7Alan L. Landay8Madeleine Durand9Cécile L. Tremblay10Petronela Ancuta11Département de Microbiologie, Infectiologie et Immunologie, Faculté de Médecine, Université de Montréal (UdeM), Montreal, QC H2X 0A9, CanadaDépartement de Microbiologie, Infectiologie et Immunologie, Faculté de Médecine, Université de Montréal (UdeM), Montreal, QC H2X 0A9, CanadaCRCHUM, Montreal, QC H2X 0A2, CanadaCRCHUM, Montreal, QC H2X 0A2, CanadaCRCHUM, Montreal, QC H2X 0A2, CanadaCRCHUM, Montreal, QC H2X 0A2, CanadaChronic Viral Illness Service and Division of Hematology, Research Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, CanadaCRCHUM, Montreal, QC H2X 0A2, CanadaRush University Medical Center, Chicago, IL 60612, USACRCHUM, Montreal, QC H2X 0A2, CanadaDépartement de Microbiologie, Infectiologie et Immunologie, Faculté de Médecine, Université de Montréal (UdeM), Montreal, QC H2X 0A9, CanadaDépartement de Microbiologie, Infectiologie et Immunologie, Faculté de Médecine, Université de Montréal (UdeM), Montreal, QC H2X 0A9, CanadaCardiovascular disease (CVD) remains an important comorbidity in people living with HIV-1 (PLWH) receiving antiretroviral therapy (ART). Our previous studies performed in the Canadian HIV/Aging Cohort Study (CHACS) (>40 years-old; Framingham Risk Score (FRS) > 5%) revealed a 2–3-fold increase in non-calcified coronary artery atherosclerosis (CAA) plaque burden, measured by computed tomography angiography scan (CTAScan) as the total (TPV) and low attenuated plaque volume (LAPV), in ART-treated PLWH (HIV+) versus uninfected controls (HIV−). In an effort to identify novel correlates of subclinical CAA, markers of intestinal damage (sCD14, LBP, FABP2); cell trafficking/inflammation (CCL20, CX3CL1, MIF, CCL25); subsets of Th17-polarized and regulatory (Tregs) CD4<sup>+</sup> T-cells, classical/intermediate/non-classical monocytes, and myeloid/plasmacytoid dendritic cells were studied in relationship with HIV and TPV/LAPV status. The TPV detection/values coincided with higher plasma sCD14, FABP2, CCL20, MIF, CX3CL1, and triglyceride levels; lower Th17/Treg ratios; and classical monocyte expansion. Among HIV<sup>+</sup>, TPV<sup>+</sup> versus TPV<sup>−</sup> exhibited lower Th17 frequencies, reduced Th17/Treg ratios, higher frequencies of non-classical CCR9<sup>low</sup>HLADR<sup>high</sup> monocytes, and increased plasma fibrinogen levels. Finally, Th17/Treg ratios and non-classical CCR9<sup>low</sup>HLADR<sup>high</sup> monocyte frequencies remained associated with TPV/LAPV after adjusting for FRS and HIV/ART duration in a logistic regression model. These findings point to Th17 paucity and non-classical monocyte abundance as novel immunological correlates of subclinical CAA that may fuel the CVD risk in ART-treated PLWH.https://www.mdpi.com/2073-4409/13/2/157HIV-1antiretroviral therapy (ART)cardiovascular disease (CVD)Th17/Treg cellsnon-classical monocytesmyeloid/plasmacytoid dendritic cells
spellingShingle Tomas Raul Wiche Salinas
Yuwei Zhang
Annie Gosselin
Natalia Fonseca Rosario
Mohamed El-Far
Ali Filali-Mouhim
Jean-Pierre Routy
Carl Chartrand-Lefebvre
Alan L. Landay
Madeleine Durand
Cécile L. Tremblay
Petronela Ancuta
Alterations in Th17 Cells and Non-Classical Monocytes as a Signature of Subclinical Coronary Artery Atherosclerosis during ART-Treated HIV-1 Infection
Cells
HIV-1
antiretroviral therapy (ART)
cardiovascular disease (CVD)
Th17/Treg cells
non-classical monocytes
myeloid/plasmacytoid dendritic cells
title Alterations in Th17 Cells and Non-Classical Monocytes as a Signature of Subclinical Coronary Artery Atherosclerosis during ART-Treated HIV-1 Infection
title_full Alterations in Th17 Cells and Non-Classical Monocytes as a Signature of Subclinical Coronary Artery Atherosclerosis during ART-Treated HIV-1 Infection
title_fullStr Alterations in Th17 Cells and Non-Classical Monocytes as a Signature of Subclinical Coronary Artery Atherosclerosis during ART-Treated HIV-1 Infection
title_full_unstemmed Alterations in Th17 Cells and Non-Classical Monocytes as a Signature of Subclinical Coronary Artery Atherosclerosis during ART-Treated HIV-1 Infection
title_short Alterations in Th17 Cells and Non-Classical Monocytes as a Signature of Subclinical Coronary Artery Atherosclerosis during ART-Treated HIV-1 Infection
title_sort alterations in th17 cells and non classical monocytes as a signature of subclinical coronary artery atherosclerosis during art treated hiv 1 infection
topic HIV-1
antiretroviral therapy (ART)
cardiovascular disease (CVD)
Th17/Treg cells
non-classical monocytes
myeloid/plasmacytoid dendritic cells
url https://www.mdpi.com/2073-4409/13/2/157
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