Macrophage Gal/GalNAc lectin 2 (MGL2)+ peritoneal antigen presenting cells during Fasciola hepatica infection are essential for regulatory T cell induction

Costa, Monique; Costa, Valeria da; Lores, Pablo; Landeira, Mercedes; Rodríguez-Zraquia, Santiago A.; Festari, María Florencia; Freire, Teresa

doi:10.1038/s41598-022-21520-w

Cited by 4 publications

(3 citation statements)

References 65 publications

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“…61 Costa et al demonstrated that depletion of M2 macrophages was associated with partial resistance to infection and increase levels of Foxp3 + Treg. 62 In a subsequent study, this group demonstrated that splenic Tregs and production of heme-oxygenase-1 (HO-1) by peritoneal antigen presenting cells depends on IL-10 activity in Fasciola infected mice. Upregulation of HO-1 decreased the production of reactive oxygen and nitrogen species and increased the number of Treg.…”

Section: Chronic Phasementioning

confidence: 99%

An Update on the Pathogenesis of Fascioliasis: What Do We Know?

Tanabe,

Caravedo,

White

et al. 2024

RRTM

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Fasciola hepatica is a trematode parasite distributed worldwide. It is known to cause disease in mammals, producing significant economic loses to livestock industry and burden to human health. After ingestion, the parasites migrate through the liver and mature in the bile ducts. A better understanding of the parasite's immunopathogenesis would help to develop efficacious therapeutics and vaccines. Currently, much of our knowledge comes from in vitro and in vivo studies in animal models. Relatively little is known about the host-parasite interactions in humans. Here, we provide a narrative review of what is currently know about the pathogenesis and host immune responses to F. hepatica summarizing the evidence available from the multiple hosts that this parasite infects.

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Section: Chronic Phasementioning

confidence: 99%

An Update on the Pathogenesis of Fascioliasis: What Do We Know?

Tanabe,

Caravedo,

White

et al. 2024

RRTM

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“…In addition, the production of immunomodulatory molecules by mMGL2+ cells is associated with an increase in clinical symptoms and Treg expansion. Thus, it seems that MGL interactions are F. hepatica's strategy to escape host immune control [159].…”

Section: • Fasciola Hepaticamentioning

confidence: 99%

Ligand Recognition by the Macrophage Galactose-Type C-Type Lectin: Self or Non-Self?—A Way to Trick the Host’s Immune System

Szczykutowicz

2023

IJMS

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The cells and numerous macromolecules of living organisms carry an array of simple and complex carbohydrates on their surface, which may be recognized by many types of proteins, including lectins. Human macrophage galactose-type lectin (MGL, also known as hMGL/CLEC10A/CD301) is a C-type lectin receptor expressed on professional antigen-presenting cells (APCs) specific to glycans containing terminal GalNAc residue, such as Tn antigen or LacdiNAc but also sialylated Tn antigens. Macrophage galactose-type lectin (MGL) exhibits immunosuppressive properties, thus facilitating the maintenance of immune homeostasis. Hence, MGL is exploited by tumors and some pathogens to trick the host immune system and induce an immunosuppressive environment to escape immune control. The aims of this article are to discuss the immunological outcomes of human MGL ligand recognition, provide insights into the molecular aspects of these interactions, and review the MGL ligands discovered so far. Lastly, based on the human fetoembryonic defense system (Hu-FEDS) hypothesis, this paper raises the question as to whether MGL-mediated interactions may be relevant in the development of maternal tolerance toward male gametes and the fetus.

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“…The role of MGL in immune regulation is not fully understood but appears to be highly dependent on the antigen structure. In some cases, glycotope interactions with MGL seem to facilitate immune escape of the pathogen via DC secretion of anti-inflammatory cytokines, − such as interleukin-10 (IL-10), which reduces the glycolytic activity of DCs or abrogates the T helper 1/2 (Th1/2) type response in favor of regulatory T cells (Treg) or T helper 17 (Th17) type responses …”

Section: Introductionmentioning

confidence: 99%

MUC1 Glycopeptide Vaccine Modified with a GalNAc Glycocluster Targets the Macrophage Galactose C-type Lectin on Dendritic Cells to Elicit an Improved Humoral Response

et al. 2023

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Mucin expression and glycosylation patterns on cancer cells differ markedly from healthy cells. Mucin 1 (MUC1) is overexpressed in several solid tumors and presents high levels of aberrant, truncated O-glycans (e.g., Tn antigen). Dendritic cells (DCs) express lectins that bind to these tumor-associated carbohydrate antigens (TACAs) to modulate immune responses. Selectively targeting these receptors with synthetic TACAs is a promising strategy to develop anticancer vaccines and to overcome TACA tolerance. In this work, we prepared, via a solid phase peptide synthesis approach, a modular tripartite vaccine candidate, incorporating a high-affinity glycocluster based on a tetraphenylethylene scaffold, to target the macrophage galactose-type lectin (MGL) on antigen presenting cells. MGL is a C-type lectin receptor that binds Tn antigens and can route them to human leukocyte antigen class II or I, making it an attractive target for anticancer vaccines. Conjugation of the glycocluster to a library of MUC1 glycopeptides bearing the Tn antigen is shown to promote uptake and recognition of the TACA by DCs via MGL. In vivo testing revealed that immunization with the newly designed vaccine construct bearing the GalNAc glycocluster induced a higher titer of anti-Tn-MUC1 antibodies compared to the TACAs alone. Additionally, the antibodies obtained bind a library of tumor-associated saccharide structures on MUC1 and MUC1-positive breast cancer cells. Conjugation of a high-affinity ligand for MGL to tumorassociated MUC1 glycopeptide antigens has a synergistic impact on antibody production.

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Macrophage Gal/GalNAc lectin 2 (MGL2)+ peritoneal antigen presenting cells during Fasciola hepatica infection are essential for regulatory T cell induction

Cited by 4 publications

References 65 publications

An Update on the Pathogenesis of Fascioliasis: What Do We Know?

An Update on the Pathogenesis of Fascioliasis: What Do We Know?

Ligand Recognition by the Macrophage Galactose-Type C-Type Lectin: Self or Non-Self?—A Way to Trick the Host’s Immune System

MUC1 Glycopeptide Vaccine Modified with a GalNAc Glycocluster Targets the Macrophage Galactose C-type Lectin on Dendritic Cells to Elicit an Improved Humoral Response

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