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

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),...

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Autores principales: Jost, Stephanie, Moreno-Nieves, Uriel Y, Garcia-Beltran, Wilfredo F, Rands, Keith, Reardon, Jeff, Toth, Ildiko, Piechocka-Trocha, Alicja, Altfeld, Marcus, Addo, Marylyn M
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3750478/
https://www.ncbi.nlm.nih.gov/pubmed/23866914
http://dx.doi.org/10.1186/1742-4690-10-74
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author Jost, Stephanie
Moreno-Nieves, Uriel Y
Garcia-Beltran, Wilfredo F
Rands, Keith
Reardon, Jeff
Toth, Ildiko
Piechocka-Trocha, Alicja
Altfeld, Marcus
Addo, Marylyn M
author_facet Jost, Stephanie
Moreno-Nieves, Uriel Y
Garcia-Beltran, Wilfredo F
Rands, Keith
Reardon, Jeff
Toth, Ildiko
Piechocka-Trocha, Alicja
Altfeld, Marcus
Addo, Marylyn M
author_sort Jost, Stephanie
collection PubMed
description 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.
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spelling pubmed-37504782013-08-24 Dysregulated Tim-3 expression on natural killer cells is associated with increased Galectin-9 levels in HIV-1 infection Jost, Stephanie Moreno-Nieves, Uriel Y Garcia-Beltran, Wilfredo F Rands, Keith Reardon, Jeff Toth, Ildiko Piechocka-Trocha, Alicja Altfeld, Marcus Addo, Marylyn M Retrovirology Research 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. BioMed Central 2013-07-18 /pmc/articles/PMC3750478/ /pubmed/23866914 http://dx.doi.org/10.1186/1742-4690-10-74 Text en Copyright © 2013 Jost et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Jost, Stephanie
Moreno-Nieves, Uriel Y
Garcia-Beltran, Wilfredo F
Rands, Keith
Reardon, Jeff
Toth, Ildiko
Piechocka-Trocha, Alicja
Altfeld, Marcus
Addo, Marylyn M
Dysregulated Tim-3 expression on natural killer cells is associated with increased Galectin-9 levels in HIV-1 infection
title Dysregulated Tim-3 expression on natural killer cells is associated with increased Galectin-9 levels in HIV-1 infection
title_full Dysregulated Tim-3 expression on natural killer cells is associated with increased Galectin-9 levels in HIV-1 infection
title_fullStr Dysregulated Tim-3 expression on natural killer cells is associated with increased Galectin-9 levels in HIV-1 infection
title_full_unstemmed Dysregulated Tim-3 expression on natural killer cells is associated with increased Galectin-9 levels in HIV-1 infection
title_short Dysregulated Tim-3 expression on natural killer cells is associated with increased Galectin-9 levels in HIV-1 infection
title_sort dysregulated tim-3 expression on natural killer cells is associated with increased galectin-9 levels in hiv-1 infection
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3750478/
https://www.ncbi.nlm.nih.gov/pubmed/23866914
http://dx.doi.org/10.1186/1742-4690-10-74
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