IL-32 Drives the Differentiation of Cardiotropic CD4+ T-Cells Carrying HIV DNA in People Living with HIV.
H RamaniA GosselinR BunetM A JenabianM SyllaA PagliuzzaC Chartrand-LefebvreJean-Pierre RoutyJ P GouletR ThomasB TrottierV Martel-LaferrièreC FortinNicolas ChomontR FromentinA LandayM DurandP AncutaM El-FarC TremblayPublished in: The Journal of infectious diseases (2023)
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.
Keyphrases
- hiv infected
- antiretroviral therapy
- tyrosine kinase
- cardiovascular disease
- human immunodeficiency virus
- hiv positive
- heart failure
- hiv aids
- oxidative stress
- hiv testing
- hiv infected patients
- cell free
- epidermal growth factor receptor
- single molecule
- circulating tumor
- machine learning
- working memory
- immune response
- dendritic cells
- metabolic syndrome
- coronary artery disease
- cell migration
- deep learning
- big data