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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2024-01-01
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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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