VAMP8-mediated NOX2 recruitment to endosomes is necessary for antigen release

Cross-presentation of foreign antigen in major histocompatibility complex (MHC) class I by dendritic cells (DCs) requires activation of the NADPH-oxidase NOX2 complex. We recently showed that NOX2 is recruited to phagosomes by the SNARE protein VAMP8 where NOX2-produced reactive oxygen species (ROS) cause lipid oxidation and membrane disruption, promoting antigen translocation into the cytosol for cross-presentation. In this study, we extend these findings by showing that VAMP8 is also involved in NOX2 trafficking to endosomes. Moreover, we demonstrate in both human and mouse DCs that absence of VAMP8 leads to decreased ROS production, lipid peroxidation and antigen translocation, and that this impairs cross-presentation. In contrast, knockdown of VAMP8 did not affect recruitment of MHC class I and the transporter associated with antigen processing 1 (TAP1) to phagosomes, although surface levels of MHC class I were reduced. Thus, in addition to a secretory role, VAMP8-mediates trafficking of NOX2 to endosomes and phagosomes and this promotes induction of cytolytic T cell immune responses. (C) 2017 The Authors. Published by Elsevier GmbH

VAMP8-mediated NOX2 recruitment to endosomes is necessary for antigen release

Dingjan I, Paardekooper LM, Verboogen DRJ, Fischer von Mollard G, ter Beest M, van den Bogaart G. VAMP8-mediated NOX2 recruitment to endosomes is necessary for antigen release. European Journal of Cell Biology. 2017;96(7):705-714.Cross-presentation of foreign antigen in major histocompatibility complex (MHC) class I by dendritic cells (DCs) requires activation of the NADPH-oxidase NOX2 complex. We recently showed that NOX2 is recruited to phagosomes by the SNARE protein VAMP8 where NOX2-produced reactive oxygen species (ROS) cause lipid oxidation and membrane disruption, promoting antigen translocation into the cytosol for cross-presentation. In this study, we extend these findings by showing that VAMP8 is also involved in NOX2 trafficking to endosomes. Moreover, we demonstrate in both human and mouse DCs that absence of VAMP8 leads to decreased ROS production, lipid peroxidation and antigen translocation, and that this impairs cross-presentation. In contrast, knockdown of VAMP8 did not affect recruitment of MHC class I and the transporter associated with antigen processing 1 (TAP1) to phagosomes, although surface levels of MHC class I were reduced. Thus, in addition to a secretory role, VAMP8-mediates trafficking of NOX2 to endosomes and phagosomes and this promotes induction of cytolytic T cell immune responses. (C) 2017 The Authors. Published by Elsevier GmbH

Correction to: Vaccination against galectin-1 promotes cytotoxic T-cell infiltration in melanoma and reduces tumor burden (Cancer Immunology, Immunotherapy, (2022), 71, 8, (2029-2040), 10.1007/s00262-021-03139-4)

The article Vaccination against galectin-1 promotes cytotoxic T-cell infltration in melanoma and reduces tumor burden, written by Julia Femel, Luuk van Hooren, Melanie Herre, Jessica Cedervall, Falk Saupe, Elisabeth J. M. Huijbers, Danielle R. J. Verboogen, Matthias Reichel, Victor L. Thijssen, Arjan W. Grifoen, Lars Hellman, Anna Dimberg and Anna-Karin Olsson, was originally published electronically on the publisher’s internet portal on 11 January 2021 without open access. With the author(s)’ decision to opt for Open Choice the copyright of the article changed on 08 February 2022 t

ENDOSOMAL AND PHAGOSOMAL SNAREs

The soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein family is of vital importance for organelle communication. The complexing of cognate SNARE members present in both the donor and target organellar membranes drives the membrane fusion required for intracellular transport. In the endocytic route, SNARE proteins mediate trafficking between endosomes and phagosomes with other endosomes, lysosomes, the Golgi apparatus, the plasma membrane, and the endoplasmic reticulum. The goal of this review is to provide an overview of the SNAREs involved in endosomal and phagosomal trafficking. Of the 38 SNAREs present in humans, 30 have been identified at endosomes and/or phagosomes. Many of these SNAREs are targeted by viruses and intracellular pathogens, which thereby reroute intracellular transport for gaining access to nutrients, preventing their degradation, and avoiding their detection by the immune system. A fascinating picture is emerging of a complex transport network with multiple SNAREs being involved in consecutive trafficking routes

Lipid peroxidation causes endosomal antigen release for cross-presentation

Dingjan I, Verboogen DRJ, Paardekooper LM, et al. Lipid peroxidation causes endosomal antigen release for cross-presentation. SCIENTIFIC REPORTS. 2016;6(1): 22064.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