Galectin-8 Enhances T cell Response by Promotion of Antigen Internalization and Processing

Prato, Cecilia A.; Carabelli, Julieta; Campetella, Oscar; Tribulatti, María Virginia

doi:10.1016/j.isci.2020.101278

Cited by 9 publications

(5 citation statements)

References 52 publications

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“…They can also directly interact with the SARS-CoV-2 viruses and affect viral replication. Alternatively, Gals may modulate antigen presentation/processing and stimulate the elicitation of T cell response in a lectin-dependent manner ( 75 ). Further studies are required to better understand the role of viral factors and Gals in the induction of cytokine release syndrome and provide evidence to better understand SARS-CoV-2 pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

Analysis of SARS-CoV-2 isolates, namely the Wuhan strain, Delta variant, and Omicron variant, identifies differential immune profiles

Shahbaz,

Bozorgmehr,

et al. 2023

Microbiol Spectr

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There is an urgent need to better understand the impact of different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants on immune response and disease dynamics to facilitate better intervention strategies. Here, we show that SARS-CoV-2 variants differentially affect host immune responses. The magnitude and quantity of cytokines and chemokines were comparable in those infected with the Wuhan strain and the Delta variant. However, individuals infected with the Omicron variant had significantly lower levels of these mediators. We also found an elevation of plasma galectins (Gal-3, Gal-8, and Gal-9) in infected individuals, in particular, in those with the original strain. Soluble galectins exert a proinflammatory role in COVID-19 pathogenesis. This was illustrated by their correlation with the plasma levels of sCD14, sCD163, enhanced TNF-α/IL-6 secretion, and increased SARS-CoV-2 infectivity in vitro . Moreover, we observed enhanced CD4 + and CD8 + T cell activation in Wuhan strain-infected individuals. Surprisingly, there was a more pronounced T cell activation in those infected with the Omicron in comparison to the Delta variant. In line with T cell activation status, we observed a more pronounced expansion of T cells expressing different co-inhibitory receptors in patients infected with the Wuhan strain, followed by the Omicron and Delta variants. Individuals infected with the Wuhan strain or the Omicron variant had a similar pattern of plasma soluble immune checkpoints. Our results imply that a milder innate immune response might be beneficial and protective in those infected with the Omicron variant. Our results provide a novel insight into the differential impact of SARS-CoV-2 variants on host immunity. IMPORTANCE There is a need to better understand how different SARS-CoV-2 variants influence the immune system and disease dynamics to facilitate the development of better vaccines and therapies. We compared immune responses in 140 SARS-CoV-2-infected individuals with the Wuhan strain, the Delta variant, or the Omicron variant. All these patients were admitted to the intensive care unit and were SARS-CoV-2 vaccination naïve. We found that SARS-CoV-2 variants differentially affect the host immune response. This was done by measuring soluble biomarkers in their plasma and examining different immune cells. Overall, we found that the magnitude of cytokine storm in individuals infected with the Wuhan strain or the Delta variant was greater than in those infected with the Omicron variant. In light of enhanced cytokine release syndrome in individuals infected with the Wuhan strain or the Delta variant, we believe that a milder innate immune response might be beneficial and protective in those infected with the Omicron variant.

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Section: Discussionmentioning

confidence: 99%

Analysis of SARS-CoV-2 isolates, namely the Wuhan strain, Delta variant, and Omicron variant, identifies differential immune profiles

Shahbaz,

Bozorgmehr,

et al. 2023

Microbiol Spectr

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“…Despite these interesting studies on the role of Gal-8, it is important to mention that its role in cancer progression is not black-and-white. Although similar to other galectins, Gal-8 can induce apoptosis in immature T cells [ 101 , 102 ], recent studies in various experimental systems by Maria Tribulatti’s group suggest that Gal-8 has important immunostimulatory functions in peripheral naïve T cells and promotes the uptake of antigens by antigen-presenting cells [ 103 , 104 ]. Interestingly, Gal-3 has been shown to inhibit the immunostimulatory effect of Gal-8 on naïve T cells [ 105 ], emphasizing the need to develop galectin inhibitors that are very specific.…”

Section: The Case Of Galectin-8mentioning

confidence: 99%

Galectins in Glioma: Current Roles in Cancer Progression and Future Directions for Improving Treatment

Ajarrag

St‐Pierre

2021

Cancers

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Traditional wisdom suggests that galectins play pivotal roles at different steps in cancer progression. Galectins are particularly well known for their ability to increase the invasiveness of cancer cells and their resistance to drug-induced cell death. They also contribute to the development of local and systemic immunosuppression, allowing cancer cells to escape the host’s immunological defense. This is particularly true in glioma, the most common primary intracranial tumor. Abnormally high production of extracellular galectins in glioma contributes to the establishment of a strong immunosuppressive environment that favors immune escape and tumor progression. Considering the recent development and success of immunotherapy in halting cancer progression, it is logical to foresee that galectin-specific drugs may help to improve the success rate of immunotherapy for glioma. This provides a new perspective to target galectins, whose intracellular roles in cancer progression have already been investigated thoroughly. In this review, we discuss the mechanisms of action of galectins at different steps of glioma progression and the potential of galectin-specific drugs for the treatment of glioma.

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“…Some additional information can be drawn from other (non-tumoral) experimental models. Indeed, galectin-8 promotes all steps of antigen presentation from antigen binding, internalization, processing [ 211 ], and maturation of dendritic cells [ 212 , 213 ]. Studies with galectin-8 deficient antigen-presenting cells confirmed the relevance of such functions in pathophysiology [ 212 ].…”

Section: Introductionmentioning

confidence: 99%

Unraveling How Tumor-Derived Galectins Contribute to Anti-Cancer Immunity Failure

Laderach

Compagno

2021

Cancers

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Current data indicates that anti-tumor T cell-mediated immunity correlates with a better prognosis in cancer patients. However, it has widely been demonstrated that tumor cells negatively manage immune attack by activating several immune-suppressive mechanisms. It is, therefore, essential to fully understand how lymphocytes are activated in a tumor microenvironment and, above all, how to prevent these cells from becoming dysfunctional. Tumors produce galectins-1, -3, -7, -8, and -9 as one of the major molecular mechanisms to evade immune control of tumor development. These galectins impact different steps in the establishment of the anti-tumor immune responses. Here, we carry out a critical dissection on the mechanisms through which tumor-derived galectins can influence the production and the functionality of anti-tumor T lymphocytes. This knowledge may help us design more effective immunotherapies to treat human cancers.

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Galectin-8 Enhances T cell Response by Promotion of Antigen Internalization and Processing

Abstract: Gal-8-glycan interactions at APC surface induce soluble antigen internalizationGal-8 and antigen are internalized together in early endosomal compartments Gal-8 favors antigen proteolytic processing and presentation in the context of MHC-II

Cited by 9 publications

References 52 publications

Analysis of SARS-CoV-2 isolates, namely the Wuhan strain, Delta variant, and Omicron variant, identifies differential immune profiles

Analysis of SARS-CoV-2 isolates, namely the Wuhan strain, Delta variant, and Omicron variant, identifies differential immune profiles

Galectins in Glioma: Current Roles in Cancer Progression and Future Directions for Improving Treatment

Unraveling How Tumor-Derived Galectins Contribute to Anti-Cancer Immunity Failure

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