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  • IL-32 Drives the Differenti...
    Ramani, Hardik; Gosselin, Annie; Bunet, Rémi; Jenabian, Mohammad-Ali; Sylla, Mohamed; Pagliuzza, Amélie; Chartrand-Lefebvre, Carl; Routy, Jean-Pierre; Goulet, Jean-Philippe; Thomas, Réjean; Trottier, Benoit; Martel-Laferrière, Valérie; Fortin, Claude; Chomont, Nicolas; Fromentin, Rémi; Landay, Alan L; Durand, Madeleine; Ancuta, Petronela; El-Far, Mohamed; Tremblay, Cecile

    The Journal of infectious diseases, 2024-May-15, 2024-05-15, 20240515, Volume: 229, Issue: 5
    Journal Article

    Interleukin 32 (IL-32) is a potent multi-isoform proinflammatory cytokine, which is upregulated in people with HIV (PWH) 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 PWH 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-naive 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 PWH.