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Orders Norzivirales and Timlovirales
Published in Paul Pumpens, Peter Pushko, Philippe Le Mercier, Virus-Like Particles, 2022
Paul Pumpens, Peter Pushko, Philippe Le Mercier
Recently, Alam et al. (2021) engineered another glycan-modified Qβ VLPs that evoked Th1 immune responses. It was examined how antigen structure can influence uptake and signaling from the C-type lectin DC-SIGN (dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin or CD209). In fact, the signaling depended on the ligand displayed on the VLP: only those particles densely functionalized with an aryl mannoside, Qβ-Man540, elicited DC maturation and induced the expression of the proinflammatory cytokines characteristic of a Th1 response. The mice immunized with a VLP bearing the aryl mannoside and a peptide antigen (Qβ-OVA-Man540) had antigen-specific responses, including the production of CD4+ T cells producing the activating cytokines interferon-γ and tumor necrosis factor-α (Alam et al. 2021). Therefore, this study strongly highlighted the utility of the DC-targeted VLPs as vaccine vehicles that induce cellular immunity. It should be noted that the basics of the appropriate methodology were elaborated on the Qβ VLPs by Ribeiro-Viana et al. (2012).
Recognition of microbe-associated molecular patterns by pattern recognition receptors
Published in Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald, Principles of Mucosal Immunology, 2020
An important feature of CLRs is their redundancy. This important feature of CLRs is best reflected in the detection of Mycobacteria tuberculosis by Dectin-1, Mincle, MR, and DC-SIGN. Receptor deletion models show that whereas loss of one of these receptors may not impact survival in response to M. tuberculosis infection, together they play a critical role in the detection and control of this life-threatening bacterial pathogen. Characteristic of PRRs, a single CLR may recognize components on multiple pathogens. For example, DC-SIGN plays a key role in the recognition and host cell entry of HIV-1 but also contributes to the recognition of cytomegalovirus, as well as dengue, ebola, hepatitis C, West Nile, and measles viruses. Not limited to virus recognition, DC-SIGN also recognizes glycan motifs in the soluble egg antigen of multiple schistosome species. Beside parasitic worm recognition, the CLRs contribute to the recognition of certain protozoa, evidenced by the critical role played by DCIR in the development of experimental cerebral malaria caused by Plasmodium berghei.
The Development of Improved Therapeutics through a Glycan- “Designer” Approach
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Dendritic cell CTL, called DC-SIGN, is an excellent example of C-type lectin receptor which recognizes high-mannose glycans and Lewis-type antigens. These receptors are used for targeted delivery to dendritic cells. Overall lectins serve as detectors for both self and non-self-molecular patterns, playing an important role in both pathogen defense system and autoimmune protection. There are many proteins of complement system that act as potential glycan receptors allowing prompt immune detection and signaling. Most of the natural complement proteins are synthesized in liver and the saccharide composition and expression levels vary between complement components, also may vary between individuals and life span of the cells. Nonetheless, most of the complement components synthesized in the liver contain sialylated, biantennary glycans, while component C3 contains only oligo-mannose type glycans.
The role of sialic acid-binding immunoglobulin-like-lectin-1 (siglec-1) in immunology and infectious disease
Published in International Reviews of Immunology, 2023
Shane Prenzler, Santosh Rudrawar, Mario Waespy, Sørge Kelm, Shailendra Anoopkumar-Dukie, Thomas Haselhorst
Ebola viruses belong to the Filoviridae family and consist of many strains which are capable of causing hemorrhagic fever [27]. Ebola viruses also utilize dendritic cells and macrophages to disseminate to the lymph nodes, liver and spleen [88]. Ebola virus dendritic cell entry involves several steps requiring multitude of receptors. DC-SIGN mediates attachment of the Ebola virus to dendritic cells by glycoprotein recognition, meanwhile TIM/TAM receptors bind phosphatidylserine on the membrane of virus facilitating viral cell entry by means of apoptotic mimicry [89–91]. From here Ebola viruses enters the cell after macropinocytosis and the viral glycoprotein is cleaved using cellular proteases like cathepsin B [27, 92]. The cleavage allows for glycoprotein recognition by endosome receptor Niemann-Pick C1, which allows the virus to enter the cytoplasm [93, 94]. It was recently discovered that in a similar way to HIV-1, ebola virus buds from host cells and incorporates GM1 gangliosides which bind Siglec-1 [27]. The role of Siglec-1 in attachment and entry of Ebola virus is poorly understood, but it has been shown that anti-Siglec-1 antibodies are able to hinder viral entry and that Siglec-1 is more prominent to the entry of the virus than other well-known receptors like DC-SIGN [27]. Currently, there are studies underway to create vaccines for Zaire ebolavirus (ZEBOV), which is the species responsible for a recent outbreak in West Africa. However, there are other species which will not be covered by vaccine efforts and Siglec-1 may represent an important therapeutic target [27].
Targeting glyco-immune checkpoints for cancer therapy
Published in Expert Opinion on Biological Therapy, 2021
Collectins are a family of soluble and membrane-situated C-type lectins [76]. Some collectins can recognize pathogen-associated patterns and mediate innate immune cell activation [76]. MGL is a macrophage and dendritic cell (DC)-associated C-type lectin recognizing N-acetyl-galactosamine residues [76]. MGL can inhibit T cell effector function by its interaction with CD45 [83]. It could potentially be targeted in the cancer setting to improve anti-cancer immunity. DC-SIGN is another C-type lectin that can regulate immune cells [76]. DC-SIGN is expressed on macrophages and DCs binding to fucose-containing glycans [84]. DC-SIGN is able to induce the secretion of immunosuppressive cytokines, thereby promoting an immunosuppressive microenvironment [84]. Recent results have also shown that DC-SIGN can bind to sialylated glycans and mediate immune suppression [85].
Aberrant fucosylation enables breast cancer clusterin to interact with dendritic cell-specific ICAM-grabbing non-integrin (DC-SIGN)
Published in OncoImmunology, 2019
Antonela Merlotti, Alvaro López Malizia, Paula Michea, Pierre-Emmanuel Bonte, Christel Goudot, María Sol Carregal, Nicolás Nuñez, Christine Sedlik, Ana Ceballos, Vassili Soumelis, Sebastián Amigorena, Jorge Geffner, Eliane Piaggio, Juan Sabatte
We next analyzed DC-SIGN expression by the different populations of DC and macrophages found in breast tumor samples using flow cytometry. The gating strategy is illustrated in Figure 4(a). As previously described,28 we identified four major DC populations: CD11c− CD123+ plasmacytoid pre-DCs, CD11c+ BDCA1+ CD14− DCs, CD11c+ BDCA1− CD14− DCs, and CD11c+ BDCA1+ CD14+ inflammatory DCs. The most prominent intratumoral myeloid cell population, however, was shown to be represented by macrophages, defined as CD11c+ BDCA1− CD14+ cells. We analyzed DC-SIGN expression on the surface of these populations by flow cytometry. As shown on Figure 4(c), DC-SIGN was only expressed on the membrane of macrophages from tumoral as well as juxtatumoral tissues, but not on the DC populations analyzed. Next, we analyzed DC-SIGN mRNA expression by RNA sequencing on each sorted population. Among all the cell populations analyzed on tumor samples, macrophages showed the highest DC-SIGN mRNA expression (Figure 4(b)).