Mentrup, Torben and Stumpff-Niggemann, Anna Yamina and Leinung, Nadja and Schlosser, Christine and Schubert, Katja and Wehner, Rebekka and Tunger, Antje and Schatz, Valentin and Neubert, Patrick and Gradtke, Ann-Christine and Wolf, Janina and Rose-John, Stefan and Saftig, Paul and Dalpke, Alexander and Jantsch, Jonathan and Schmitz, Marc and Fluhrer, Regina and Jacobsen, Ilse D. and Schroeder, Bernd (2022) Phagosomal signalling of the C-type lectin receptor Dectin-1 is terminated by intramembrane proteolysis. NATURE COMMUNICATIONS, 13 (1): 1880. ISSN , 2041-1723
Full text not available from this repository. (Request a copy)Abstract
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. 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 beta-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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | BETA-GLUCAN RECEPTOR; PEPTIDASE-LIKE 2A; B-CELL; PATTERN-RECOGNITION; PROTEASE SPPL2A; DENDRITIC CELLS; NEGATIVE REGULATION; TNF-ALPHA; ACTIVATION; INDUCTION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 27 Feb 2024 14:41 |
| Last Modified: | 27 Feb 2024 14:41 |
| URI: | https://pred.uni-regensburg.de/id/eprint/58051 |
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