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Cited by 277Antifungal resistance and susceptibilityFungal and yeast genetics researchAutophagy in Disease and Therapy

Phagocytosis and Intracellular Fate of Aspergillus fumigatus Conidia in Alveolar Macrophages

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Ibrahim-Granet, O., Philippe, B., Boleti, H., Boisvieux-Ulrich, E., Grenet, D., Stern, M., Latgé, J. P.·2003·Infection and Immunity
DOI 10.1128/iai.71.2.891-903.2003PMC PMC145364
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Abstract

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 and late endosomal/lysosomal pathways within 30 to 60 min of phagocytosis, regarded as a normal phagosome maturation process.

    “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]

  • AMs efficiently eliminate phagocytosed Aspergillus conidia within 24 h in acidified phagolysosomes.

    “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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Research works printed but not linked: 2

  1. [18]Ciechanover, A., A. L. Schwartz, A. Dautry-Varsat, and H. F. Lodish. 1983. Kinetics of internalization and recycling of transferrin and the transferrin receptors in a human hepatoma cell line. J. Biol. Chem. 9:9681-9689. [PubMed] [Google Scholar]
  2. [69]Tjelle, T. E., T. Lovdal, and T. Berg. 2000. Phagosome dynamics and function. Bioessays 22:255-263. [DOI] [PubMed] [Google Scholar]

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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
DOI
10.1128/iai.71.2.891-903.2003
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
Licence
journals.asm.org/non-commercial-tdm-license (tdm)
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
  • Health Sciences › Medicine › Epidemiology › 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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