Journal article
Galectin-9 is rapidly released during acute HIV-1 infection and remains sustained at high levels despite viral suppression even in elite controllers.
- Abstract:
- Galectin-9 (Gal-9) is a β-galactosidase-binding lectin that promotes apoptosis, tissue inflammation, and T cell immune exhaustion, and alters HIV infection in part through engagement with the T cell immunoglobulin mucin domain-3 (Tim-3) receptor and protein disulfide isomerases (PDI). Gal-9 was initially thought to be an eosinophil attractant, but is now known to mediate multiple complex signaling events that affect T cells in both an immunosuppressive and inflammatory manner. To understand the kinetics of circulating Gal-9 levels during HIV infection we measured Gal-9 in plasma during HIV acquisition, in subjects with chronic HIV infection with differing virus control, and in uninfected individuals. During acute HIV infection, circulating Gal-9 was detected as early as 5 days after quantifiable HIV RNA and tracked plasma levels of interleukin (IL)-10, tumor necrosis factor (TNF)-α, and IL-1β. In chronic HIV infection, Gal-9 levels positively correlated with plasma HIV RNA levels (r=0.29; p=0.023), and remained significantly elevated during suppressive antiretroviral therapy (median: 225.3 pg/ml) and in elite controllers (263.3 pg/ml) compared to age-matched HIV-uninfected controls (54 pg/ml). Our findings identify Gal-9 as a novel component of the first wave of the cytokine storm in acute HIV infection that is sustained at elevated levels in virally suppressed subjects and suggest that Gal-9:Tim-3 crosstalk remains active in elite controllers and antiretroviral (ARV)-suppressed subjects, potentially contributing to ongoing inflammation and persistent T cell dysfunction.
- Publication status:
- Published
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Authors
- Publisher:
- Mary Ann Liebert Inc.
- Journal:
- AIDS research and human retroviruses More from this journal
- Volume:
- 30
- Issue:
- 7
- Pages:
- 654-664
- Publication date:
- 2014-07-01
- DOI:
- EISSN:
-
1931-8405
- ISSN:
-
0889-2229
- Language:
-
English
- Pubs id:
-
pubs:463272
- UUID:
-
uuid:c1be35e1-e176-46b6-a5a5-36ae1886c5ba
- Local pid:
-
pubs:463272
- Source identifiers:
-
463272
- Deposit date:
-
2014-06-17
Terms of use
- Copyright date:
- 2014
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