Journal ArticleDOI
Differential high-affinity interaction of dectin-1 with natural or synthetic glucans is dependent upon primary structure and is influenced by polymer chain length and side-chain branching.
Elizabeth L. Adams,Peter J. Rice,Bridget M. Graves,Harry E. Ensley,Hai Yu,Gordon D. Brown,Siamon Gordon,Mario A. Monteiro,Erzsebet Papp-Szabo,Douglas W. Lowman,Trevor D. Power,Michael F. Wempe,David L. Williams +12 more
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TLDR
This study examined the effect of glucan structure on recognition and binding by murine recombinant Dectin-1 with a library of natural product and synthetic (1→3)-β/(1→6)-β-glucans as well as nonglucan polymers and found that glucan derived from a saprophytic yeast was recognized with higher affinity than glucanderived from the pathogen Candida albicans.Abstract:
Glucans are structurally diverse fungal biopolymers that stimulate innate immunity and are fungal pathogen-associated molecular patterns. Dectin-1 is a C-type lectin-like pattern recognition receptor that binds glucans and induces innate immune responses to fungal pathogens. We examined the effect of glucan structure on recognition and binding by murine recombinant Dectin-1 with a library of natural product and synthetic (1-->3)-beta/(1-->6)-beta-glucans as well as nonglucan polymers. Dectin-1 is highly specific for glucans with a pure (1-->3)-beta-linked backbone structure. Although Dectin-1 is highly specific for (1-->3)-beta-d-glucans, it does not recognize all glucans equally. Dectin-1 differentially interacted with (1-->3)-beta-d-glucans over a very wide range of binding affinities (2.6 mM-2.2 pM). One of the most striking observations that emerged from this study was the remarkable high-affinity interaction of Dectin-1 with certain glucans (2.2 pM). These data also demonstrated that synthetic glucan ligands interact with Dectin-1 and that binding affinity increased in synthetic glucans containing a single glucose side-chain branch. We also observed differential recognition of glucans derived from saprophytes and pathogens. We found that glucan derived from a saprophytic yeast was recognized with higher affinity than glucan derived from the pathogen Candida albicans. Structural analysis demonstrated that glucan backbone chain length and (1-->6)-beta side-chain branching strongly influenced Dectin-1 binding affinity. These data demonstrate: 1) the specificity of Dectin-1 for glucans; 2) that Dectin-1 differentiates between glucan ligands based on structural determinants; and 3) that Dectin-1 can recognize and interact with both natural product and synthetic glucan ligands.read more
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Journal ArticleDOI
Activation of the innate immune receptor Dectin-1 upon formation of a /`phagocytic synapse/'
Helen S. Goodridge,Christopher N. Reyes,Courtney A. Becker,Tamiko R. Katsumoto,Jun Ma,Andrea J. Wolf,Nandita Bose,Anissa S.H. Chan,Andrew S. Magee,Michael E. Danielson,Arthur Weiss,John P. Vasilakos,David M. Underhill,David M. Underhill +13 more
TL;DR: The ‘phagocytic synapse’ now provides a model mechanism by which innate immune receptors can distinguish direct microbial contact from detection of microbes at a distance, thereby initiating direct cellular antimicrobial responses only when they are required.
Journal ArticleDOI
β‐glucan recognition by the innate immune system
TL;DR: This review explores what is currently known about β‐glucan recognition and how this recognition stimulates immune responses, and special emphasis is placed on Dectin‐1, as the authors know the most about how this key β‐ glucan receptor translates recognition into intracellular signaling, stimulates cellular responses,and participates in orchestrating the adaptive immune response.
Journal ArticleDOI
Beta-glucan: an ideal immunostimulant in aquaculture (a review).
Dharmendra Kumar Meena,Pronob Das,Shailesh Kumar,Subhash C. Mandal,A. K. Prusty,Soibam Khogen Singh,M. S. Akhtar,Bijay Kumar Behera,Kundan Kumar,Asim K. Pal,S.C. Mukherjee +10 more
TL;DR: This review highlights β-glucan as an immunostimulant, its effective dosages, and route of administration and furthermore provides an outline on role of β- glucan in enhancing growth, survival, and protection against infectious pathogens pertaining to fishes and shellfishes.
Journal ArticleDOI
Tasting the fungal cell wall.
TL;DR: A comprehensive understanding of the interactions between the host membrane receptors and the fungal cell wall components is still lacking and thefungal adhesins playing a role in adhesion to host have been only explored in yeasts.
Journal ArticleDOI
Differential pathways regulating innate and adaptive antitumor immune responses by particulate and soluble yeast-derived β-glucans
Chunjian Qi,Chunjian Qi,Yihua Cai,Lacey Gunn,Chuanlin Ding,Bing Li,Goetz H. Kloecker,Keqing Qian,John Vasilakos,Shinobu Saijo,Yoichiro Iwakura,John R. Yannelli,Jun Yan +12 more
TL;DR: It is shown that yeast-derived particulate β-glucan activated dendritic cells (DCs) and macrophages via a C-type lectin receptor dectin-1 pathway, revealing the importance of different preparations of β- glucans in the adjuvant therapy and allow for the rational design of immunotherapeutic protocols usable in clinical trials.
References
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Journal ArticleDOI
Immune recognition. A new receptor for beta-glucans.
Gordon D. Brown,Siamon Gordon +1 more
TL;DR: This work identifies this unknown receptor on macrophages as dectin-1 (ref. 2), a finding that provides new insights into the innate immune recognition of β-glucans.
Journal ArticleDOI
Dectin-1 Mediates the Biological Effects of β-Glucans
Gordon D. Brown,Jurgen Herre,David L. Williams,Janet A. Willment,Andrew S J Marshall,Siamon Gordon +5 more
TL;DR: It is shown that Dectin-1 mediates the production of TNF-α in response to zymosan and live fungal pathogens, an activity that occurs at the cell surface and requires the cytoplasmic tail and immunoreceptor tyrosine activation motif of Dect in addition to Toll-like receptor (TLR)-2 and Myd88.