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NADPH oxidase controls phagosomal pH and antigen cross-presentation in human dendritic cells
Open accessAbstract
The phagocyte NADPH oxidase (NOX2) is critical for the bactericidal activity of phagocytic cells and plays a major role in innate immunity. We showed recently that NOX2 activity in mouse dendritic cells (DCs) prevents acidification of phagosomes, promoting antigen cross-presentation. Inorder to investigate the role of NOX2 in the regulation of the phagosomal pH in human DCs, we analyzed the production of reactive oxygen species (ROS) and the phagosomal/endosomal pH in monocyte-derived DCs and macrophages (MØs) from healthy donors or patients with chronic granulomatous disease (CGD). As expected, we found that human MØs acidify their phagosomes more efficiently than human DCs. Accordingly, the expression of the vacuolar proton ATPase (V-H+-ATPase) was higher in MØs than in DCs. Phagosomal ROS production, however, was also higher in MØs than in DCs, due to higher levels of gp91phox expression and recruitment to phagosomes. In contrast, in the absence of active NOX2, the phagosomal and endosomal pH decreased. Both in the presence of a NOX2 inhibitor and in DCs derived from patients with CGD, the cross-presentation of 2 model tumor antigens was impaired. We conclude that NOX2 activity participates in the regulation of the phagosomal and endosomal pH in human DCs, and is required for efficient antigen cross-presentation.
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“Dendritic cells (DC) express little NOX2 and consequently have a lower O2•− and ROS production after activation [179].”
From Superoxide Anion Chemistry—Its Role at the Core of the Innate Immunity (2023) · cites this paper as [179]
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Metadata
- Authors
- Mantegazza, A. R., Savina, A., Vermeulen, M., Pérez, L., Geffner, J., Hermine, O., Rosenzweig, S. D., Faure, F., & Amigorena, S.
- Affiliations
- Inserm (FR)
- Instituto de Investigaciones Hematológicas, Academia Nacional de Medicina, Buenos Aires, Argentina;
- Garrahan Hospital (AR)
- Academia Nacional de Medicina (AR)
- Hôpital Necker-Enfants Malades (FR)
- ORCID
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2008-12-01
- Volume
- 112
- Issue
- 12
- Pages
- 4712-4722
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- PMC
- PMC2597138
- OpenAlex
- W2093168274
- Cited by
- 329
- References
- 34
- Citations by year
- 2026: 14 · 2025: 16 · 2024: 17 · 2023: 26 · 2022: 23 · 2021: 22 · 2020: 28 · 2019: 17 · 2018: 22 · 2017: 18 · 2016: 15 · 2015: 18 · 2014: 8 · 2013: 15 · 2012: 28
- FWCI
- 5.84
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- CONICET Digital (CONICET) (submittedVersion, cc-by-nc-sa)
- Funders
- Institut National de la Santé et de la Recherche Médicale
- Consejo Nacional de Investigaciones Científicas y Técnicas
- National Institutes of Health
- Directorate for Biological Sciences
- Fogarty International Center (R01TW006644)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- NADPH oxidase, NOX2, dendritic cells, phagosomal pH, cross-presentation, reactive oxygen species, gp91phox, vacuolar ATPase, chronic granulomatous disease, monocyte-derived macrophages, endosomal pH, innate immunity
- MeSH terms
- NADPH Oxidase 2, Acid-Base Equilibrium, Adolescent, Adult, Cells, Cultured, Child, Child, Preschool, Dendritic Cells, Humans, Hydrogen-Ion Concentration, Macrophages, Membrane Glycoproteins, Phagosomes, Antigen Presentation, NADPH Oxidases, Cross-Priming, Young Adult
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