Identification and Biological Activity of Synthetic Macrophage Inducible C-Type Lectin Ligands

Braganza, Chriselle D.; Teunissen, Thomas; Timmer, Mattie S. M.; Stocker, Bridget L.

doi:10.3389/fimmu.2017.01940

Cited by 36 publications

(27 citation statements)

References 96 publications

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“…Thus, our findings further illustrate species‐specific differences that may exist with regard to Mincle expression 17,46 . Lastly, as functional changes to Mincle agonists can further enhance the type 1 helper immune response, 17,47,48 this highlights the potential of developing additional Mincle agonists as anticancer adjuvants.…”

Section: Discussionsupporting

confidence: 53%

“…In addition to TLR ligands, other classes of ligands that exhibit potential as anticancer agents include trehalose glycolipids 11 and monosodium urate (MSU) crystals 12,13 . Trehalose glycolipids, such as trehalose dimycolate (TDM) and its C22‐acyl chain derivate, trehalose dibehenate (TDB), are recognized by the macrophage‐inducible C‐type lectin (Mincle, Clec4e), 14,15 which is expressed on myeloid cells and which recognizes damage‐associated molecular patterns and pathogen‐associated molecular patterns 15–17 . Upon binding of TDM or TDB to Mincle, the Syk and Card9–Bcl10–MALT1 inflammasome pathways are activated, which ultimately leads to the cellular production of cytokines and chemokines and a type 1 helper immune response 14,16,18,19 .…”

Section: Introductionmentioning

confidence: 99%

“…While the anticancer activity of MSU + TDB appears promising, species‐specific differences have been observed for Mincle ligands 17,19,23 . This raises the question as to whether the TDB effect translates to human cells—particularly as studies investigating the effect of TDB on cells of human origin are rare 19,23 .…”

Section: Introductionmentioning

confidence: 99%

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The coadministration of trehalose dibehenate and monosodium urate crystals promotes an antitumor phenotype in human‐derived myeloid cells

et al. 2020

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Trehalose dibehenate (TDB), a ligand for the macrophage-inducible C-type lectin, has shown promise as an adjuvant for preventative vaccines and also as an anticancer agent in murine assays. The potential for TDB to affect the antitumor immune response of human myeloid cells, however, has not been studied. We investigated the effect of the adjuvants TDB and monosodium urate (MSU) crystals on the protumor or antitumor immune phenotype of human monocytes, macrophages and monocyte-derived dendritic cells (Mo-DCs). TDB treatment alone led to an inflammatory response in all three cell types, which was most pronounced when using human monocytes, with MSU augmenting this response. TDB also decreased cell surface markers associated with a protumorigenic phenotype, with MSU showing some ability to augment this response. Notably, a significant reduction in CD115 was observed for all antigen-presenting cells upon TDB or MSU + TDB treatment. The potential to increase the antigen-presenting capabilities of the myeloid cells was also observed upon treatment with TDB and MSU + TDB, as indicated by the upregulation of cell surface markers such as CD86 for all three cell types and a favorable ratio of interleukin (IL)-12p40 to IL-10 for monocytes stimulated with MSU + TDB. There was no significant production of IL-12p40 by Mo-DC; however, in a mixed lymphocyte assay, MSU + TDB costimulation of Mo-DC led to a significant increase in CD4 + T-cell numbers and in the IL-12p40-to-IL-10 ratio. Taken together, these findings show for the first time the potential of MSU + TDB costimulation to favor a tumor-suppressive phenotype in human-derived myeloid cells.

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Section: Discussionsupporting

confidence: 53%

Section: Introductionmentioning

confidence: 99%

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The coadministration of trehalose dibehenate and monosodium urate crystals promotes an antitumor phenotype in human‐derived myeloid cells

et al. 2020

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“…The proposed recognition site for the lipid chains of TDB is the major hydrophobic pocket of the Mincle receptor (a type of CLR). Thus, the lipid moieties also play a role in the formulation’s immune stimulating activity [ 171 ]. The presence of two fatty acids (5–14 carbons) is crucial for TDB potency [ 172 ].…”

Section: Carbohydrate-based Adjuvantsmentioning

confidence: 99%

Carbohydrate Immune Adjuvants in Subunit Vaccines

et al. 2020

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Modern subunit vaccines are composed of antigens and a delivery system and/or adjuvant (immune stimulator) that triggers the desired immune responses. Adjuvants mimic pathogen-associated molecular patterns (PAMPs) that are typically associated with infections. Carbohydrates displayed on the surface of pathogens are often recognized as PAMPs by receptors on antigen-presenting cells (APCs). Consequently, carbohydrates and their analogues have been used as adjuvants and delivery systems to promote antigen transport to APCs. Carbohydrates are biocompatible, usually nontoxic, biodegradable, and some are mucoadhesive. As such, carbohydrates and their derivatives have been intensively explored for the development of new adjuvants. This review assesses the immunological functions of carbohydrate ligands and their ability to enhance systemic and mucosal immune responses against co-administered antigens. The role of carbohydrate-based adjuvants/delivery systems in the development of subunit vaccines is discussed in detail.

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“…CLRs are a large family of proteins that are divided into 17 groups based on functional and structural characteristics. They contain an extracellular recognition domain that recognizes a wide range of microbial and fungal carbohydrates and lipids . CLRs also contain a signal transmembrane domain and a cytoplasm domain.…”

Section: Introductionmentioning

confidence: 99%

Expression and function of macrophage-inducible C-type lectin (Mincle) in inflammation driven parturition in fetal membranes and myometrium

Lim

Lappas

2019

Clinical and Experimental Immunology

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The pivotal role of inflammatory processes in human parturition is well known, but not completely understood. We have performed a study to examine the role of macrophage-inducible C-type lectin (Mincle) in inflammation-associated parturition. Using human samples, we show that spontaneous labour is associated with up-regulated Mincle expression in the myometrium and fetal membranes. Mincle expression was also increased in fetal membranes and myometrium in the presence of pro-labour mediators, the proinflammatory cytokines interleukin (IL)-1B and tumour necrosis factor (TNF), and Toll-like receptor (TLR) ligands fsl-1, poly(I:C), lipopolysaccharide (LPS) and flagellin. These clinical studies are supported by mouse studies, where an inflammatory challenge in a mouse model of preterm birth increased Mincle expression in the uterus. Importantly, elimination of Mincle decreased the effectiveness of proinflammatory cytokines and TLR ligands to induce the expression of pro-labour mediators; namely, proinflammatory cytokines and chemokines, contraction-associated proteins and prostaglandins, and extracellular matrix remodelling enzymes, matrix metalloproteinases. The data presented in this study suggest that Mincle is required when inflammatory activation precipitates parturition.

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Identification and Biological Activity of Synthetic Macrophage Inducible C-Type Lectin Ligands

Cited by 36 publications

References 96 publications

The coadministration of trehalose dibehenate and monosodium urate crystals promotes an antitumor phenotype in human‐derived myeloid cells

The coadministration of trehalose dibehenate and monosodium urate crystals promotes an antitumor phenotype in human‐derived myeloid cells

Carbohydrate Immune Adjuvants in Subunit Vaccines

Expression and function of macrophage-inducible C-type lectin (Mincle) in inflammation driven parturition in fetal membranes and myometrium

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