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Sci Rep. 2016 Feb 24;6:22064. doi: 10.1038/srep22064.

Lipid peroxidation causes endosomal antigen release for cross-presentation.

Author information

1
Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, 6525 GA, the Netherlands.
2
Department of Chemistry, Bielefeld University, Bielefeld, 33501, Germany.
3
Department of Pediatrics, Radboud University Medical Center, Nijmegen, 6525 GA, the Netherlands.

Abstract

Dendritic cells (DCs) present foreign antigen in major histocompatibility complex (MHC) class I molecules to cytotoxic T cells in a process called cross-presentation. An important step in this process is the release of antigen from the lumen of endosomes into the cytosol, but the mechanism of this step is still unclear. In this study, we show that reactive oxygen species (ROS) produced by the NADPH-oxidase complex NOX2 cause lipid peroxidation, a membrane disrupting chain-reaction, which in turn results in antigen leakage from endosomes. Antigen leakage and cross-presentation were inhibited by blocking ROS production or scavenging radicals and induced when using a ROS-generating photosensitizer. Endosomal antigen release was impaired in DCs from chronic granulomatous disease (CGD) patients with dysfunctional NOX2. Thus, NOX2 induces antigen release from endosomes for cross-presentation by direct oxidation of endosomal lipids. This constitutes a new cellular function for ROS in regulating immune responses against pathogens and cancer.

PMID:
26907999
PMCID:
PMC4764948
DOI:
10.1038/srep22064
[Indexed for MEDLINE]
Free PMC Article

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