Activation of the innate immune receptor Dectin-1 upon formation of a 'phagocytic synapse'
| Autor: | Christopher N. Reyes, Courtney A. Becker, Nandita Bose, Andrew S. Magee, Helen S. Goodridge, Michael E. Danielson, Anissa S.H. Chan, Andrea J. Wolf, David M. Underhill, Tamiko R. Katsumoto, Jun Ma, Arthur Weiss, John P. Vasilakos |
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| Rok vydání: | 2010 |
| Předmět: |
Cell signaling
beta-Glucans Immunological Synapses Phagocytosis Nerve Tissue Proteins Saccharomyces cerevisiae PTPRC Microbiology 03 medical and health sciences Mice 0302 clinical medicine Cell Wall Animals Humans Lectins C-Type Receptor Cells Cultured 030304 developmental biology 0303 health sciences Multidisciplinary Innate immune system biology CLEC7A Macrophages Receptor-Like Protein Tyrosine Phosphatases Class 3 Models Immunological Membrane Proteins Immunity Innate Cell biology Receptor-Like Protein Tyrosine Phosphatases Solubility biology.protein Leukocyte Common Antigens Signal transduction Reactive Oxygen Species 030215 immunology Signal Transduction |
| Zdroj: | Nature. 472(7344) |
| ISSN: | 1476-4687 |
| Popis: | Innate immune cells must be able to distinguish between direct binding to microbes and detection of components shed from the surface of microbes located at a distance. Dectin-1 (also known as CLEC7A) is a pattern-recognition receptor expressed by myeloid phagocytes (macrophages, dendritic cells and neutrophils) that detects β-glucans in fungal cell walls and triggers direct cellular antimicrobial activity, including phagocytosis and production of reactive oxygen species (ROS). In contrast to inflammatory responses stimulated upon detection of soluble ligands by other pattern-recognition receptors, such as Toll-like receptors (TLRs), these responses are only useful when a cell comes into direct contact with a microbe and must not be spuriously activated by soluble stimuli. In this study we show that, despite its ability to bind both soluble and particulate β-glucan polymers, Dectin-1 signalling is only activated by particulate β-glucans, which cluster the receptor in synapse-like structures from which regulatory tyrosine phosphatases CD45 and CD148 (also known as PTPRC and PTPRJ, respectively) are excluded (Supplementary Fig. 1). 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. |
| Databáze: | OpenAIRE |
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