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SHIP-1 Couples to the Dectin-1 hemITAM and Selectively Modulates Reactive Oxygen Species Production in Dendritic Cells in Response to Candida albicans.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2015 Nov 01; Vol. 195 (9), pp. 4466-4478. Date of Electronic Publication: 2015 Sep 28. - Publication Year :
- 2015
-
Abstract
- Dectin-1 (Clec7a) is a paradigmatic C-type lectin receptor that binds Syk through a hemITAM motif and couples sensing of pathogens such as fungi to induction of innate responses. Dectin-1 engagement triggers a plethora of activating events, but little is known about the modulation of such pathways. Trying to define a more precise picture of early Dectin-1 signaling, we explored the interactome of the intracellular tail of the receptor in mouse dendritic cells. We found unexpected binding of SHIP-1 phosphatase to the phosphorylated hemITAM. SHIP-1 colocalized with Dectin-1 during phagocytosis of zymosan in a hemITAM-dependent fashion. Moreover, endogenous SHIP-1 relocated to live or heat-killed Candida albicans-containing phagosomes in a Dectin-1-dependent manner in GM-CSF-derived bone marrow cells (GM-BM). However, SHIP-1 absence in GM-BM did not affect activation of MAPK or production of cytokines and readouts dependent on NF-κB and NFAT. Notably, ROS production was enhanced in SHIP-1-deficient GM-BM treated with heat-killed C. albicans, live C. albicans, or the specific Dectin-1 agonists curdlan or whole glucan particles. This increased oxidative burst was dependent on Dectin-1, Syk, PI3K, phosphoinositide-dependent protein kinase 1, and NADPH oxidase. GM-BM from CD11c∆SHIP-1 mice also showed increased killing activity against live C. albicans that was dependent on Dectin-1, Syk, and NADPH oxidase. These results illustrate the complexity of myeloid C-type lectin receptor signaling, and how an activating hemITAM can also couple to intracellular inositol phosphatases to modulate selected functional responses and tightly regulate processes such as ROS production that could be deleterious to the host.<br /> (Copyright © 2015 by The American Association of Immunologists, Inc.)
- Subjects :
- Amino Acid Motifs genetics
Amino Acid Sequence
Animals
Blotting, Western
Bone Marrow Cells immunology
Bone Marrow Cells metabolism
Bone Marrow Cells microbiology
Candida albicans physiology
Dendritic Cells metabolism
Granulocyte-Macrophage Colony-Stimulating Factor immunology
Granulocyte-Macrophage Colony-Stimulating Factor metabolism
Host-Pathogen Interactions immunology
Inositol Polyphosphate 5-Phosphatases
Lectins, C-Type genetics
Lectins, C-Type metabolism
Macrophages immunology
Macrophages metabolism
Macrophages microbiology
Mice, Knockout
Microscopy, Confocal
Molecular Sequence Data
NF-kappa B immunology
NF-kappa B metabolism
NFATC Transcription Factors immunology
NFATC Transcription Factors metabolism
Phagocytosis immunology
Phagosomes immunology
Phagosomes metabolism
Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases
Phosphoric Monoester Hydrolases genetics
Phosphoric Monoester Hydrolases metabolism
Protein Binding immunology
Reactive Oxygen Species metabolism
Signal Transduction immunology
Amino Acid Motifs immunology
Candida albicans immunology
Dendritic Cells immunology
Lectins, C-Type immunology
Phosphoric Monoester Hydrolases immunology
Reactive Oxygen Species immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 195
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 26416276
- Full Text :
- https://doi.org/10.4049/jimmunol.1402874