Activation of the innate immune receptor Dectin-1 upon formation of a “phagocytic synapse”
By H. Goodridge, C. Reyes, Courtney A. Becker, T. Katsumoto, Jun Ma, Andrea J. Wolf, N. Bose, Anissa S. H. Chan, A. Magee, Michael E. Danielson and 3 more. Nature, 2011
807 citations recorded by the source corpus.
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.
Subfields: Immunology, Microbiology
View Paper: https://www.semanticscholar.org/paper/1aae42cc6741e113af17d45ec19bc3e7e6c88e09
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Citations in the corpus
- Innate Immune Pattern Recognition: A Cell Biological Perspective (2015, neutral): “This feature may help to differentiate ligands directly associated with a microbe and those released from a distance (136).”
- The inflammasome: an integrated view (2011, background): “Local contact of a phagocyte with a pathogen leads to the formation of a phagocytic synapse, which is characterized by focal clustering of receptors and exclusion of inhibitory molecules at the site of pathogen contact (93).”
- Phagocytosis: An Immunobiologic Process. (2016, background): “The Phagocytic Synapse: Role of Dectin-1, FcR, and Integrins Schematic representation of Dectin-1 clustering at the site of contact with particulate zymosan; CD45 and CD148 tyrosine phosphatases are excluded from the contact zone (reproduced from Goodridge et al., 2011, with permission).”