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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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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: Boleti, H.
Stern, M.
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: green
europepmc.org
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
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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Phagocytosis and Intracellular Fate of Aspergillus fumigatus Conidia in Alveolar Macrophages

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