Étude du rôle de l'interleukine-32 dans l'infection à VIH-1
HIV-1 slow progressors constitute a rare population of subjects who remain asymptomatic for many years without antiretroviral therapy. Among this population, some individuals will lose control of their infection after several years of immunological control.  Our laboratory has analyzed the differential expression profile of various proteins and molecular pathways associated with the loss of control of HIV infection.  The pro-inflammatory cytokine interleukin-32 alpha and delta isoforms significantly decreased in slow progressors as they were losing control of their infection.  Furthermore, previous studies have attributed to IL-32 both antiviral property against HIV-1 and immunosuppressive properties that can induce an environment conducive to HIV-1 replication. This project addresses the role of IL-32 in HIV-1 disease progression with a particular emphasis on slow progressors.  We compared the levels of IL-32 in HIV-1 positive versus HIV-1 negative subjects and evaluated the role of this cytokine using longitudinal studies. We observed that levels of IL-32 remains higher in HIV-positive compared to HIV-negative subjects.  Also, HIV-1 infection leads to increased level of IL-32.  In addition, after one year of antiretroviral therapy, IL-32 plasma levels remain significantly higher than those of HIV-negative subjects.  As expected, the levels of IL-32 increased as slow progressors lost control of their infection.  A high plasma concentration of IL-32 predicts:  1) an increase in plasma levels of sCD14 as well as pro-inflammatory cytokine IL-6, 2) a decrease in CD4 cell count and an increase in viral load.  High plasma CCL5 predicted a low concentration of IL-32.  The alpha isoform of IL-32 is elevated in the plasma of HIV negative subjects while IL-32 gamma appears to induce a pro-inflammatory and immunosuppressive environment. We conclude that increased IL-32 levels are associated with progression of HIV-1 disease and could be used as a biomarker for assessing HIV-1 prognosis.
Cd14-soluble Interleukine-6 Ccl5 Interleukine-10 Hiv-1 Slow-progressors Interleukin-32 Soluble-cd14 Interleukin-6 Interleukin-10