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Phagocytosis and Intracellular Fate of Aspergillus fumigatus Conidia in Alveolar Macrophages
Open accessAbstract
Aspergillus fumigatus is the most prevalent airborne fungal pathogen responsible for fatal invasive aspergillosis in immunocompromised patients. Upon arrival in the lung alveolus, conidia of A. fumigatus are phagocytosed by alveolar macrophages, the major phagocytic cells of the lung. Engulfment and intracellular trafficking of A. fumigatus conidia in alveolar macrophages of two different origins, the murine cell line MH-S and human pulmonary alveolar macrophages, were analyzed by electron microscopy and immunofluorescence. Phagocytosis of A. fumigatus conidia required actin polymerization and phosphatidylinositol 3-kinase activity. Fusion of A. fumigatus phagosomes with early and late endosomes was shown by immunolabeling with specific markers for the transferrin receptor, early endosome antigen, and Rab7. Maturation of A. fumigatus phagolysosomes was monitored by using a fixable acidotropic probe, LysoTracker Red DND-99, and an anti-cathepsin D antibody. Bafilomycin A-induced inhibition of lysosomal acidification abolished the conidial killing by the macrophages. These data suggest that the maturation of A. fumigatus phagosomes results from fusion with the compartments of the endocytic pathway and that the killing of conidia depends on phagolysosome acidification. A model for the phagocytosis of A. fumigatus conidia by alveolar macrophages is proposed on the basis of these results.
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“Initial studies on Aspergillus phagosome biogenesis demonstrated rapid acquisition of markers of the early (EEA-1, Rab5, and transferrin receptor) and late endosomal/lysosomal (Rab7, LAMP-1, CD63, and cathepsin D) pathways within 30 to 60 min of phagocytosis, which was regarded as a normal phagosome maturation process (203, 238).”
From Aspergillus fumigatus and Aspergillosis in 2019 (2019) · cites this paper as [238]
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“AMs efficiently eliminate phagocytosed Aspergillus conidia within 24 h in acidified phagolysosomes (203, 220, 238, 239).”
From Aspergillus fumigatus and Aspergillosis in 2019 (2019) · cites this paper as [238]
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Metadata
- Authors
- Ibrahim-Granet, O., Philippe, B., Boleti, H., Boisvieux-Ulrich, E., Grenet, D., Stern, M., & Latgé, J. P.
- Affiliations
- Institut Pasteur (FR)
- Centre National de la Recherche Scientifique (FR)
- Laboratoire de Cytophysiologie et Toxicologie Cellulaire, Université Paris VII, Paris
- Hôpital Foch (FR)
- Unité des Aspergillus, Institut Pasteur
- Corresponding author
- Ibrahim-Granet, O.
- ORCID
- Venue
- Infection and Immunity
- Publisher
- American Society for Microbiology
- Published
- 2003-02
- Volume
- 71
- Issue
- 2
- Pages
- 891-903
- ISSN
- 0019-9567 (ISSN-L)
- 1098-5522
- PMC
- PMC145364
- OpenAlex
- W2097192281
- Cited by
- 277
- References
- 77
- Citations by year
- 2026: 7 · 2025: 8 · 2024: 6 · 2023: 12 · 2022: 13 · 2021: 19 · 2020: 6 · 2019: 6 · 2018: 16 · 2017: 13 · 2016: 8 · 2015: 14 · 2014: 18 · 2013: 12 · 2012: 18
- FWCI
- 7.38
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Infection and Immunity (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Keywords
- Aspergillus fumigatus, conidia, alveolar macrophages, phagocytosis, phagosome maturation, endosomal membrane fusion, actin polymerization, phosphatidylinositol 3-kinase, invasive aspergillosis
- MeSH terms
- Actins, Animals, Aspergillus fumigatus, Cell Line, Cells, Cultured, Humans, Hydrogen-Ion Concentration, Microscopy, Electron, Microscopy, Electron, Scanning, Phagocytosis, Phagosomes, Macrophages, Alveolar, Phosphatidylinositol 3-Kinases, Mice
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