IL-32 Drives the Differentiation of Cardiotropic CD4+ T-Cells Carrying HIV DNA in People Living with HIV

H Ramani; A Gosselin; R Bunet; M A Jenabian; M Sylla; A Pagliuzza; C Chartrand-Lefebvre; J P Routy; J P Goulet; R Thomas; B Trottier; V Martel-Laferrière; C Fortin; N Chomont; R Fromentin; A Landay; M Durand; P Ancuta; M El-Far; C Tremblay

doi:10.1093/infdis/jiad576

IL-32 Drives the Differentiation of Cardiotropic CD4+ T-Cells Carrying HIV DNA in People Living with HIV

J Infect Dis. 2023 Dec 19:jiad576. doi: 10.1093/infdis/jiad576. Online ahead of print.

Authors

H Ramani^{1

2}, A Gosselin², R Bunet^{1

2}, M A Jenabian^{1

3}, M Sylla², A Pagliuzza², C Chartrand-Lefebvre^{2

4}, J P Routy⁵, J P Goulet⁶, R Thomas⁷, B Trottier⁸, V Martel-Laferrière^{1

2}, C Fortin⁹, N Chomont^{1

2}, R Fromentin^{1

2}, A Landay¹⁰, M Durand^{2

11}, P Ancuta^{1

2}, M El-Far², C Tremblay^{1

2}

Affiliations

¹ Département de Microbiologie, Infectiologie et Immunologie, Faculté de Médecine, Université de Montréal, QC, Canada.
² Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, Québec, Canada.
³ Department of Biological Sciences, Université du Québec, Montréal (UQAM), Montréal, QC, Canada.
⁴ Département de Radiologie, Radio-oncologie et Médecine Nucléaire, Faculté de Médecine, Université de Montréal, Montréal, QC, Canada.
⁵ Research Institute of McGill University Health Centre, Montréal, QC, Canada.
⁶ CellCarta, Montréal, QC, Canada.
⁷ Clinique médicale l'Actuel, Montréal, QC, Canada.
⁸ Centre de médecine urbaine du Quartier latin, Montréal, QC, Canada.
⁹ CHUM: Centre hospitalier de l'Université de Montréal, Montréal, Québec, Canada.
¹⁰ Department of Internal Medicine, Rush University Medical Center, Chicago, IL, USA.
¹¹ Département de Médecine, Faculté de Médecine, Université de Montréal, QC, Canada.

PMID: 38113908
DOI: 10.1093/infdis/jiad576

Abstract

IL-32 is a potent multi-isoform proinflammatory cytokine, which is upregulated in people living with HIV (PLWH) and is associated with cardiovascular disease (CVD) risk. However, the impact of IL-32 isoforms on CD4 T-cell cardiotropism, a mechanism potentially contributing to heart inflammation, remains unknown. Here we show that IL-32 isoforms β and γ induce the generation of CCR4 + CXCR3 + double positive (DP) memory CD4 T-cell subpopulation expressing the tyrosine kinase receptor c-Met, a phenotype associated with heart-homing of T-cells. Our ex vivo studies on PLWH show that the frequency of DP CD4 T-cells is significantly higher in individuals with, compared to individuals without, subclinical atherosclerosis and that DP cells from antiretroviral-naïve and treated individuals are highly enriched with HIV DNA. Together, these data demonstrate that IL-32 isoforms have the potential to induce heart-homing of HIV-infected CD4 T-cells, which may further aggravate heart inflammation and CVD in PLWH.

Keywords: CD4 T-cells; Cardiovascular disease; HIV; IL-32; heart-homing; inflammation.