Phagosomal signalling of the C-type lectin receptor Dectin-1 is terminated by intramembrane proteolysis.


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
06 04 2022
Historique:
received: 23 11 2020
accepted: 14 03 2022
entrez: 7 4 2022
pubmed: 8 4 2022
medline: 9 4 2022
Statut: epublish

Résumé

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.

Identifiants

pubmed: 35388002
doi: 10.1038/s41467-022-29474-3
pii: 10.1038/s41467-022-29474-3
pmc: PMC8987071
doi:

Substances chimiques

Lectins, C-Type 0
Ligands 0
Receptors, Pattern Recognition 0
dectin 1 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1880

Informations de copyright

© 2022. The Author(s).

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Auteurs

Torben Mentrup (T)

Institute of Physiological Chemistry, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.

Anna Yamina Stumpff-Niggemann (AY)

Biochemical Institute, Christian-Albrechts-University of Kiel, Kiel, Germany.

Nadja Leinung (N)

Institute of Physiological Chemistry, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.

Christine Schlosser (C)

Biochemistry and Molecular Biology, Institute of Theoretical Medicine, Medical Faculty, University of Augsburg, Augsburg, Germany.

Katja Schubert (K)

Research Group Microbial Immunology, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Jena, Germany.

Rebekka Wehner (R)

Institute of Immunology, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
National Center for Tumor Diseases (NCT), Partner Site Dresden, Dresden, Germany.
German Cancer Consortium (DKTK), Partner Site Dresden, Dresden, and German Cancer Research Center (DKFZ), Heidelberg, Germany.

Antje Tunger (A)

Institute of Immunology, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
National Center for Tumor Diseases (NCT), Partner Site Dresden, Dresden, Germany.

Valentin Schatz (V)

Institute of Clinical Microbiology and Hygiene, University Hospital of Regensburg and University of Regensburg, Regensburg, Germany.

Patrick Neubert (P)

Institute of Clinical Microbiology and Hygiene, University Hospital of Regensburg and University of Regensburg, Regensburg, Germany.

Ann-Christine Gradtke (AC)

Institute of Physiological Chemistry, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.

Janina Wolf (J)

Biochemical Institute, Christian-Albrechts-University of Kiel, Kiel, Germany.

Stefan Rose-John (S)

Biochemical Institute, Christian-Albrechts-University of Kiel, Kiel, Germany.

Paul Saftig (P)

Biochemical Institute, Christian-Albrechts-University of Kiel, Kiel, Germany.

Alexander Dalpke (A)

Institute of Medical Microbiology and Virology, University Hospital Carl Gustav Carus, Medical Faculty, Technische Universität Dresden, Dresden, Germany.

Jonathan Jantsch (J)

Institute of Clinical Microbiology and Hygiene, University Hospital of Regensburg and University of Regensburg, Regensburg, Germany.

Marc Schmitz (M)

Institute of Immunology, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
National Center for Tumor Diseases (NCT), Partner Site Dresden, Dresden, Germany.
German Cancer Consortium (DKTK), Partner Site Dresden, Dresden, and German Cancer Research Center (DKFZ), Heidelberg, Germany.

Regina Fluhrer (R)

Biochemistry and Molecular Biology, Institute of Theoretical Medicine, Medical Faculty, University of Augsburg, Augsburg, Germany.

Ilse D Jacobsen (ID)

Research Group Microbial Immunology, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Jena, Germany.
Institute of Microbiology, Friedrich Schiller University, Jena, Germany.

Bernd Schröder (B)

Institute of Physiological Chemistry, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany. bernd.schroeder@tu-dresden.de.

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