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Dysregulated Tim-3 expression on natural killer cells is associated with increased Galectin-9 levels in HIV-1 infection

2013; BioMed Central; Volume: 10; Issue: 1 Linguagem: Inglês

10.1186/1742-4690-10-74

1742-4690

Stéphanie Jost, Uriel Y. Moreno‐Nieves, Wilfredo F. García-Beltrán, Keith Rands, Jeff Reardon, Ildikó Y. Tóth, Alicja Piechocka‐Trocha, Marcus Altfeld, Marylyn M. Addo,

Galectins and Cancer Biology

Abstract Background Natural killer (NK) cells constitutively express high levels of Tim-3, an immunoregulatory molecule recently proposed to be a marker for mature and functional NK cells. Whether HIV-1 infection modulates the expression of Tim-3 on NK cells, or the levels of its ligand Galectin-9 (Gal-9), and how signaling through these molecules affects the NK cell response to HIV-1 remains inadequately understood. Results We analyzed Tim-3 and Gal-9 expression in a cohort of 85 individuals with early and chronic HIV-1 infection, and in 13 HIV-1 seronegative control subjects. HIV-1 infection was associated with reduced expression of Tim-3 on NK cells, which was normalized by HAART. Plasma concentrations of Gal-9 were higher in HIV-1-infected individuals than in healthy individuals. Interestingly, Gal-9 expression in immune cells was significantly elevated in early infection, with monocytes and dendritic cells displaying the highest expression levels, which correlated with HIV-1 viral loads. In vitro , Gal-9 triggered Tim-3 downregulation on NK cells as well as NK cell activation. Conclusions Our data suggest that high expression levels of Gal-9 during early HIV-1 infection can lead to enhanced NK cell activity, possibly allowing for improved early control of HIV-1. In contrast, persistent Gal-9 production might impair Tim-3 activity and contribute to NK cell dysfunction in chronic HIV-1 infection.