Contribution of N-Linked Oligosaccharides to the Expression and Functions of .BETA.-Glucan Receptor, Dectin-1

Kato, Yuichi; Adachi, Yoshiyuki; Ohno, Naohito

doi:10.1248/bpb.29.1580

Cited by 41 publications

(27 citation statements)

References 32 publications

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“…Mouse Dectin-1 has 2 potential Nlinked glycosylation sites within the CRD while the human β-glucan receptor lacks these sites but contains one potential site in the stalk region. Although glycosylation is not required for Dectin-1 ligand binding, a recent study by Kato et al indicated that maximum cell surface expression and NF-κB activation is dependent on the presence of the glycosylation sites in the context of Dectin-1 expression studies in HEK293 cells [18]. Crystal structural data also indicates that Dectin-1 maintains a metal binding site characteristic of the snake venom coagulation factor IX binding protein.…”

Section: Dectin-1 Structure and Functionmentioning

confidence: 99%

The Pattern Recognition Receptor Dectin-1: From Fungi to Mycobacteria

Schorey¹,

Lawrence

2008

CDT

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The ability of the innate immune system to quickly recognize and respond to an invading pathogen is essential for controlling the infection. For this purpose, cells of the immune system express receptors which recognize evolutionarily conserved structures expressed by various pathogens but absent from host cells. In this review we focus on the non-classical C-type lectin receptors including Dectin-1 whose role has been extensively characterized in the recognition and response to fungal pathogens. Dectin-1 is a type II transmembrane protein which binds β-1,3 and β-1,6 glucans. It is expressed on most cells of the innate immune system and has been implicated in phagocytosis as well as killing of fungi by macrophages, neutrophils and dendritic cells. The Dectin-1 cytoplasmic tail contains an immunoreceptor tyrosine based activation motif (ITAM) that signals in part through the spleen tyrosine kinase and in collaboration with Toll-like receptors. Although the main research focus has been on Dectin-1's role as a fungal and yeast pathogen recognition receptor, more recent studies suggest that Dectin-1 may have a broader function in pathogen recognition including a role in directing a macrophage response to mycobacterial infections.

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Section: Dectin-1 Structure and Functionmentioning

confidence: 99%

The Pattern Recognition Receptor Dectin-1: From Fungi to Mycobacteria

Schorey¹,

Lawrence

2008

CDT

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“…Dectin-1 contains a single extracellular carbohydrate-recognition domain, an immunoreceptor tyrosine activation-like motif in its cytoplasmic tail (3), and is N-glycosylated, a modification that contributes to its surface expression and function (4). The cellular responses observed upon activation of dectin-1 include phagocytosis and an oxidative burst, as well as the production of eicosanoids, inflammatory cytokines, and chemokines (1,5).…”

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confidence: 99%

Fungal recognition is mediated by the association of dectin-1 and galectin-3 in macrophages

Esteban

Popp

Vyas

et al. 2011

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

137

115

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Dectin-1, the major β-glucan receptor in leukocytes, triggers an effective immune response upon fungal recognition. Here we use sortase-mediated transpeptidation, a technique that allows placement of a variety of probes on a polypeptide backbone, to monitor the behavior of labeled functional dectin-1 in live cells with and without fungal challenge. Installation of probes on dectin-1 by sortagging permitted highly specific visualization of functional protein on the cell surface and its subsequent internalization upon ligand presentation. Retrieval of sortagged dectin-1 expressed in macrophages uncovered a unique interaction between dectin-1 and galectin-3 that functions in the proinflammatory response of macrophages to pathogenic fungi. When macrophages expressing dectin-1 are exposed to Candida albicans mutants with increased exposure of β-glucan, the loss of galectin-3 dramatically accentuates the failure to trigger an appropriate TNF-α response.pattern-recognition receptors | sortase A | polysaccharide

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“…23 Neither of these two polymorphisms was predicted to affect glycosylation sites. 24 It is unknown if those polymorphisms in the B6 gene affect the function of the receptor.…”

Section: Discussionmentioning

confidence: 99%

Susceptibility to Coccidioides species in C57BL/6 mice is associated with expression of a truncated splice variant of Dectin-1 (Clec7a)

et al. 2008

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Coccidioides posadasii spherules stimulate macrophages to make cytokines via TLR-2 and Dectin-1. We used formalin-killed spherules and 1,3-beta-glucan purified from spherules to stimulate elicited peritoneal macrophages and myeloid dendritic cells (mDCs) from susceptible (C57BL/6) and resistant (DBA/2) mouse strains. DBA/2 macrophages produced more TNF-alpha and IL-6 than macrophages from C57BL/6 mice, and the amount of TNF-alpha made was dependent on both TLR2 and Dectin-1. DCs from C57BL/6 mice made more IL-10 and less IL-23p19 and IL-12p70 than did DBA/2 DC. These responses were inhibited by a monoclonal antibody to Dectin-1. DBA/2 mice expressed full-length Dectin-1, whereas C57BL/6 mice spliced out exon 3, which encodes most of the stalk. RAW cells transduced to express the full-length Dectin-1 responded better to FKS than cells expressing truncated Dectin-1. We compared the isoform of Dectin-1 expressed by 34 C57BL/6 X DBA/2 recombinant inbred (BXD RI) lines with their susceptibility to Coccidioides immitis. In 25 of 34 RI lines susceptibility or resistance corresponded to short or full-length isoforms, respectively. These results suggest that alternative splicing of the Dectin-1 gene contributes to susceptibility of C57BL/6 mice to coccidioidomycosis, and affects the cytokine responses of macrophages and mDCs to spherules.

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Contribution of N-Linked Oligosaccharides to the Expression and Functions of .BETA.-Glucan Receptor, Dectin-1

Cited by 41 publications

References 32 publications

The Pattern Recognition Receptor Dectin-1: From Fungi to Mycobacteria

The Pattern Recognition Receptor Dectin-1: From Fungi to Mycobacteria

Fungal recognition is mediated by the association of dectin-1 and galectin-3 in macrophages

Susceptibility to Coccidioides species in C57BL/6 mice is associated with expression of a truncated splice variant of Dectin-1 (Clec7a)

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