C-type lectin-like receptors of the dectin-1 cluster : ligands and signaling pathways

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National strategy for health research and innovation

In 2011, the Malta Council for Science and Technology (MCST) commissioned the Development of a dedicated strategy for health research and innovation in line with its mandate from Government to identify areas of national priority and design and to also implement strategic approaches to enhance economic competitiveness and quality of life. The Strategy was drawn up by a steering group which also included people from outside the health sector, to ensure that it also keeps note of the economic side of things.peer-reviewe

C-type lectin receptors of the Dectin-1 cluster : Physiological roles and involvement in disease

Acknowledgements: We apologise to our many colleagues whose valuable work we could not cite due to space constraints. Funding was provided by the Wellcome Trust (102705, 097377), the Medical Research Council Centre for Medical Mycology and the University of Aberdeen (MR/N006364/1). KT received a research fellowship from Jikei University School of Medicine.Peer reviewedPublisher PD

Identification and Characterization of a Novel Human Myeloid Inhibitory C-type Lectin-like Receptor (MICL) That Is Predominantly Expressed on Granulocytes and Monocytes

Inhibitory and activatory C-type lectin-like receptors play an important role in immunity through the regulation of leukocytes. Here, we report the identification and characterization of a novel myeloid inhibitory C-type lectin-like receptor (MICL) whose expression is primarily restricted to granulocytes and monocytes. This receptor, which contains a single C-type lectin-like domain and a cytoplasmic immunoreceptor tyrosine-based inhibitory motif, is related to LOX-1 (lectin-like receptor for oxidized low density lipoprotein-1) and the β-glucan receptor (Dectin-1) and is variably spliced and highly N-glycosylated. We demonstrate that it preferentially associates with the signaling phosphatases SHP-1 and SHP-2, but not with SHIP. Novel chimeric analyses with a construct combining MICL and the β-glucan receptor show that MICL can inhibit cellular activation through its cytoplasmic immunoreceptor tyrosine-based inhibitory motff. These data suggest that MICL is a negative regulator of granulocyte and monocyte function

Dectin-1 Is A Major β-Glucan Receptor On Macrophages

Zymosan is a β-glucan– and mannan-rich particle that is widely used as a cellular activator for examining the numerous responses effected by phagocytes. The macrophage mannose receptor (MR) and complement receptor 3 (CR3) have historically been considered the major macrophage lectins involved in the nonopsonic recognition of these yeast-derived particles. Using specific carbohydrate inhibitors, we show that a β-glucan receptor, but not the MR, is a predominant receptor involved in this process. Furthermore, nonopsonic zymosan binding was unaffected by genetic CD11b deficiency or a blocking monoclonal antibody (mAb) against CR3, demonstrating that CR3 was not the β-glucan receptor mediating this activity. To address the role of the recently described β-glucan receptor, Dectin-1, we generated a novel anti–Dectin-1 mAb, 2A11. Using this mAb, we show here that Dectin-1 was almost exclusively responsible for the β-glucan–dependent, nonopsonic recognition of zymosan by primary macro-phages. These findings define Dectin-1 as the leukocyte β-glucan receptor, first described over 50 years ago, and resolves the long-standing controversy regarding the identity of this important molecule. Furthermore, these results identify Dectin-1 as a new target for examining the immunomodulatory properties of β-glucans for therapeutic drug design

Synthesis of the fungal metabolite YWA1 and related constructs as tools to study MelLec-mediated immune response to Aspergillus infections

Funding Sources Funding was provided by the Wellcome Trust (102705, 097377), the Medical Research Council Centre for Medical Mycology and the University of Aberdeen (MR/N006364/1). ACKNOWLEDGMENT We thank Ian Fraser Flow Cytometry and Microscopy and Histology facilities, University of Aberdeen.Peer reviewedPostprin

Signalling through MyD88 drives surface expression of the mycobacterial receptors MCL (Clecsf8, Clec4d) and Mincle (Clec4e) following microbial stimulation

Acknowledgements We would like to thank the staff of the animal facility for their support and care for our animals. Funding was provided by the Wellcome Trust (102705) and Medical Research Council (UK) (MR/J004820/1) and a University of Aberdeen Studentship to BK.Peer reviewedPostprintPublisher PD

Characterization of antifungal C-type lectin receptor expression on murine epithelial and endothelial cells in mucosal tissues

Funding Information: We thank P. Asamaphan, A. Clark, and B. Kerscher for providing NIH overexpression cell lines, S. Yamasaki for the anti‐Mincle antibody, the staff of the University of Aberdeen animal facility for the care for our animals, and the Iain Fraser Cytometry Centre at the University of Aberdeen for their assistance. This work was supported by funding from the Wellcome Trust (102705, 217163), the Medical Research Council Centre for Medical Mycology, and the University of Exeter (MR/N006364/2).Peer reviewedPublisher PD

The Earth Microbiome Project: Meeting report of the "1 EMP meeting on sample selection and acquisition" at Argonne National Laboratory October 6 2010.

This report details the outcome the first meeting of the Earth Microbiome Project to discuss sample selection and acquisition. The meeting, held at the Argonne National Laboratory on Wednesday October 6(th) 2010, focused on discussion of how to prioritize environmental samples for sequencing and metagenomic analysis as part of the global effort of the EMP to systematically determine the functional and phylogenetic diversity of microbial communities across the world