Galectin-9 and IL-21 Mediate Cross-regulation between Th17 and Treg Cells during Acute Hepatitis C

Kared, Hassen; Fabre, Thomas; Bédard, Nathalie; Bruneau, Julie; Shoukry, Naglaa H.

doi:10.1371/journal.ppat.1003422

Cited by 131 publications

(141 citation statements)

References 80 publications

Supporting

Mentioning

134

Contrasting

Unclassified

Order By: Relevance

“…Furthermore, in vitro studies have found that Gal-9 induces differentiation of naive T cells to Treg cells, and suppresses differentiation to Th17 cells. 47,48,75 Given the multiple functions of Gal-9 in regulating CD4 + T cell responses, 48 this may be in part driven by Gal-9. 48,[76][77][78] Overall, our results demonstrate that Gal-9 levels are an early biomarker of HIV infection and likely track HIV viremia through primary infection and then persist into chronic infection even in subjects exhibiting good viral control.…”

Section: Discussionmentioning

confidence: 99%

Galectin-9 Is Rapidly Released During Acute HIV-1 Infection and Remains Sustained at High Levels Despite Viral Suppression Even in Elite Controllers

Tandon

Chew²,

Byron³

et al. 2014

AIDS Research and Human Retroviruses

View full text Add to dashboard Cite

Galectin-9 (Gal-9) is a b-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)-a, and IL-1b. 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.

show abstract

Section: Discussionmentioning

confidence: 99%

Galectin-9 Is Rapidly Released During Acute HIV-1 Infection and Remains Sustained at High Levels Despite Viral Suppression Even in Elite Controllers

Tandon

Chew²,

Byron³

et al. 2014

AIDS Research and Human Retroviruses

View full text Add to dashboard Cite

show abstract

“…HCV acutely infected subjects were recruited among high-risk HCV-seronegative injection drug users participating in the Montreal Hepatitis C Cohort at the Saint-Luc Hospital of the University of Montreal Health Center as previously described (44). Blood samples were processed and analyzed as previously described (45). The institutional ethics committee at the University of Montreal Hospital Research Center approved the human study (SL05.014).…”

Section: Methodsmentioning

confidence: 99%

IL2Rβ-dependent signals drive terminal exhaustion and suppress memory development during chronic viral infection

Beltra

Bourbonnais

Bédard

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

Exhaustion of CD8+ T cells severely impedes the adaptive immune response to chronic viral infections. Despite major advances in our understanding of the molecular regulation of exhaustion, the cytokines that directly control this process during chronicity remain unknown. We demonstrate a direct impact of IL-2 and IL-15, two common gamma-chain-dependent cytokines, on CD8+ T-cell exhaustion. Common to both cytokine receptors, the IL-2 receptor β (IL2Rβ) chain is selectively maintained on CD8 + T cells during chronic lymphocytic choriomeningitis virus and hepatitis C virus infections. Its expression correlates with exhaustion severity and identifies terminally exhausted CD8 + T cells both in mice and humans. Genetic ablation of the IL2Rβ chain on CD8 + T cells restrains inhibitory receptor induction, in particular 2B4 and Tim-3; precludes terminal differentiation of highly defective PD-1 hi effectors; and rescues memory T-cell development and responsiveness to IL-7-dependent signals. Together, we ascribe a previously unexpected role to IL-2 and IL-15 as instigators of CD8 + T-cell exhaustion during chronic viral infection.CD8 T cell | IL-2 | IL-15 | exhaustion | memory T cell

show abstract

“…CD26? Th17 cells capable of producing IL-21 was reported in patients who spontaneously cleared HCV [94]; the functional relevance if this result needs to be further explored.…”

Section: T Cell Responses In Chronic Hcv Infectionmentioning

confidence: 99%

Host–virus interactions in hepatitis B and hepatitis C infection

Yoshio

Kanto

2016

J Gastroenterol

View full text Add to dashboard Cite

Hepatitis B virus (HBV) and hepatitis C virus (HCV) are among the most endemic pathogens worldwide, with more than 500 million people globally currently infected with these viruses. These pathogens can cause acute and chronic hepatitis that progress to liver cirrhosis or hepatocellular carcinoma. Both viruses utilize multifaceted strategies to evade the host surveillance system and fall below the immunological radar. HBV has developed specific strategies to evade recognition by the innate immune system and is acknowledged to be a stealth virus. However, extensive research has revealed that HBV is recognized by dendritic cells (DCs) and natural killer (NK) cells. Indoleamine-2, 3-dioxygenase is an enforcer of sequential immune reactions in acute hepatitis B, and this molecule has been shown to be induced by the interaction of HBV-infected hepatocytes, DCs, and NK cells. The interleukin-28B genotype has been reported to influence HCV eradication either therapeutically or spontaneously, but the biological function of its gene product, a type-III interferon (IFN-k3), remains to be elucidated. Human BDCA3 ? DCs have also been shown to be a potent producer of IFN-k3 in HCV infection, suggesting the possibility that BDCA3 ? DCs could play a key role in developing therapeutic HCV vaccine. Here we review the current state of research on immune responses against HBV and HCV infection, with a specific focus on innate immunity. A comprehensive study based on clinical samples is urgently needed to improve our understanding of the immune mechanisms associated with viral control and thus to develop novel immune modulatory therapies to cure chronic HBV and HCV infection.

show abstract

Galectin-9 and IL-21 Mediate Cross-regulation between Th17 and Treg Cells during Acute Hepatitis C

Cited by 131 publications

References 80 publications

Galectin-9 Is Rapidly Released During Acute HIV-1 Infection and Remains Sustained at High Levels Despite Viral Suppression Even in Elite Controllers

Galectin-9 Is Rapidly Released During Acute HIV-1 Infection and Remains Sustained at High Levels Despite Viral Suppression Even in Elite Controllers

IL2Rβ-dependent signals drive terminal exhaustion and suppress memory development during chronic viral infection

Host–virus interactions in hepatitis B and hepatitis C infection

Contact Info

Product

Resources

About