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Phagosomal signalling of the C-type lectin receptor Dectin-1 is terminated by intramembrane proteolysis
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Phagosomal signalling of the C-type lectin receptor Dectin-1 is terminated by intramembrane proteolysis
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Journal Article
Phagosomal signalling of the C-type lectin receptor Dectin-1 is terminated by intramembrane proteolysis
2022
Overview
Sensing of pathogens by pattern recognition receptors (PRR) is critical to initiate protective host defence reactions. However, activation of the immune system has to be carefully titrated to avoid tissue damage necessitating mechanisms to control and terminate PRR signalling. Dectin-1 is a PRR for fungal β-glucans on immune cells that is rapidly internalised after ligand-binding. Here, we demonstrate that pathogen recognition by the Dectin-1a isoform results in the formation of a stable receptor fragment devoid of the ligand binding domain. This fragment persists in phagosomal membranes and contributes to signal transduction which is terminated by the intramembrane proteases Signal Peptide Peptidase-like (SPPL) 2a and 2b. Consequently, immune cells lacking SPPL2b demonstrate increased anti-fungal ROS production, killing capacity and cytokine responses. The identified mechanism allows to uncouple the PRR signalling response from delivery of the pathogen to degradative compartments and identifies intramembrane proteases as part of a regulatory circuit to control anti-fungal immune responses.
Dectin-1 is a critical component of the innate sensing repertoire which is involved in pattern based recognition of fungal pathogens. Here the authors show that intramembrane proteolysis is involved in the regulation of the antifungal host response by termination of the phagosomal signalling of Dectin-1.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/106
/ 13/109
/ 13/31
/ 13/89
/ 13/95
/ 14/19
/ 38/77
/ 64/60
/ 82/29
/ Binding
/ Circuits
/ Fungi
/ Glucans
/ Humanities and Social Sciences
/ Lectins, C-Type - metabolism
/ Ligands
/ Pattern recognition receptors
/ Receptors, Pattern Recognition - metabolism
/ Science
/ β-Glucan
