Oxidation inhibits autophagy protein deconjugation from phagosomes to sustain MHC class II restricted antigen presentation
| Autor: | Deepti Talwar, Christian Münz, Laure-Anne Ligeon, Maria Pena-Francesch, Nicolás Gonzalo Núñez, Liliana D. Vanoaica, Tobias P. Dick |
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| Přispěvatelé: | University of Zurich, Münz, Christian |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Phagocytosis Science Antigen presentation General Physics and Astronomy 610 Medicine & health 1600 General Chemistry chemical and pharmacologic phenomena 10263 Institute of Experimental Immunology Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 0302 clinical medicine Antigen 1300 General Biochemistry Genetics and Molecular Biology Macroautophagy Phagosome MHC class II Multidisciplinary NADPH oxidase biology Antigen processing Chemistry Autophagy General Chemistry 3100 General Physics and Astronomy Cell biology 030104 developmental biology biology.protein 570 Life sciences 030217 neurology & neurosurgery |
| Zdroj: | Nature Communications, Vol 12, Iss 1, Pp 1-13 (2021) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | LC3-associated phagocytosis (LAP) contributes to a wide range of cellular processes and notably to immunity. The stabilization of phagosomes by the macroautophagy machinery in human macrophages can maintain antigen presentation on MHC class II molecules. However, the molecular mechanisms involved in the formation and maturation of the resulting LAPosomes are not completely understood. Here, we show that reactive oxygen species (ROS) produced by NADPH oxidase 2 (NOX2) stabilize LAPosomes by inhibiting LC3 deconjugation from the LAPosome cytosolic surface. NOX2 residing in the LAPosome membrane generates ROS to cause oxidative inactivation of the protease ATG4B, which otherwise releases LC3B from LAPosomes. An oxidation-insensitive ATG4B mutant compromises LAP and thereby impedes sustained MHC class II presentation of exogenous Candida albicans antigens. Redox regulation of ATG4B is thereby an important mechanism for maintaining LC3 decoration of LAPosomes to support antigen processing for MHC class II presentation. LC3-associated phagocytosis (LAP) is a non-canonical use of the autophagy machinery that can contribute to immune responses. Here, the authors describe the mechanism by which ROS production regulates LAPosome stabilization sustaining MHC II dependent antigen presentation. |
| Databáze: | OpenAIRE |
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