Oxidized phagosomal NOX2 complex is replenished from lysosomes.

Autor: Dingjan I; Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen 6525 GA, The Netherlands., Linders PT; Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen 6525 GA, The Netherlands., van den Bekerom L; Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen 6525 GA, The Netherlands., Baranov MV; Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen 6525 GA, The Netherlands., Halder P; Department of Neurobiology, Max-Planck Institute for Biophysical Chemistry, Göttingen 37077, Germany., Ter Beest M; Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen 6525 GA, The Netherlands., van den Bogaart G; Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen 6525 GA, The Netherlands Geert.vandenBogaart@Radboudumc.nl.
Jazyk: angličtina
Zdroj: Journal of cell science [J Cell Sci] 2017 Apr 01; Vol. 130 (7), pp. 1285-1298. Date of Electronic Publication: 2017 Feb 15.
DOI: 10.1242/jcs.196931
Abstrakt: In dendritic cells, the NADPH oxidase 2 complex (NOX2) is recruited to the phagosomal membrane during antigen uptake. NOX2 produces reactive oxygen species (ROS) in the lumen of the phagosome that kill ingested pathogens, delay antigen breakdown and alter the peptide repertoire for presentation to T cells. How the integral membrane component of NOX2, cytochrome b 558 (which comprises CYBB and CYBA), traffics to phagosomes is incompletely understood. In this study, we show in dendritic cells derived from human blood-isolated monocytes that cytochrome b 558 is initially recruited to the phagosome from the plasma membrane during phagosome formation. Cytochrome b 558 also traffics from a lysosomal pool to phagosomes and this is required to replenish oxidatively damaged NOX2. We identified syntaxin-7, SNAP23 and VAMP8 as the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins mediating this process. Our data describe a key mechanism of how dendritic cells sustain ROS production after antigen uptake that is required to initiate T cell responses.
(© 2017. Published by The Company of Biologists Ltd.)
Databáze: MEDLINE
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