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Aspergillus fumigatus Triggers Inflammatory Responses by Stage-Specific β-Glucan Display
Open accessAbstract
Inhalation of fungal spores (conidia) occurs commonly and, in specific circumstances, can result in invasive disease. We investigated the murine inflammatory response to conidia of Aspergillus fumigatus, the most common invasive mold in immunocompromised hosts. In contrast to dormant spores, germinating conidia induce neutrophil recruitment to the airways and TNF-alpha/MIP-2 secretion by alveolar macrophages. Fungal beta-glucans act as a trigger for the induction of these inflammatory responses through their time-dependent exposure on the surface of germinating conidia. Dectin-1, an innate immune receptor that recognizes fungal beta-glucans, is recruited in vivo to alveolar macrophage phagosomes that have internalized conidia with exposed beta-glucans. Antibody-mediated blockade of Dectin-1 partially inhibits TNF-alpha/MIP-2 induction by metabolically active conidia. TLR-2- and MyD88-mediated signals provide an additive contribution to macrophage activation by germinating conidia. Selective responsiveness to germinating conidia provides the innate immune system with a mechanism to restrict inflammatory responses to metabolically active, potentially invasive fungal spores.
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“Significant advances have been made in elucidating the main innate immune players and effector pathways for efficient control of Aspergillus infection in mouse models with the use of transgenic mice (189–202).”
From Aspergillus fumigatus and Aspergillosis in 2019 (2019) · cites this paper as [194]
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“The discovery of selective activation of Dectin-1/Syk signaling during germination of Aspergillus conidia due to stage-specific surface exposure of β-glucan (194, 246, 247) and the ability of PRR to regulate phagosome maturation (248) provided the conceptual framework of pathogen-associated molecular patterns (PAMPs) masking as a mechanism employed by fungi to escape macrophage killing.”
From Aspergillus fumigatus and Aspergillosis in 2019 (2019) · cites this paper as [194]
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Citations
Cites
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Aspergillus fumigatus and Aspergillosis in 2019
Latgé, J.-P., & Chamilos, G. (2019) · Clinical Microbiology Reviews · doi:10.1128/cmr.00140-18 · Cited by 1,400
Dectin-1 is required for β-glucan recognition and control of fungal infection
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Dyken, S. J. V., & Locksley, R. M. (2013) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032712-095906 · Cited by 743
Metadata
- Authors
- Hohl, T. M., Van Epps, H. L., Rivera, A., Morgan, L. A., Chen, P. L., Feldmesser, M., & Pamer, E. G.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Albert Einstein College of Medicine (US)
- Corresponding author
- Pamer, Eric G
- Venue
- PLoS Pathogens
- Publisher
- Public Library of Science (PLoS)
- Published
- 2005-11-18
- Volume
- 1
- Issue
- 3
- Pages
- e30
- ISSN
- 1553-7366 (ISSN-L)
- 1553-7374
- PMC
- PMC1287910
- OpenAlex
- W2041414113
- Cited by
- 428
- References
- 46
- Citations by year
- 2026: 7 · 2025: 8 · 2024: 13 · 2023: 17 · 2022: 11 · 2021: 12 · 2020: 20 · 2019: 19 · 2018: 14 · 2017: 24 · 2016: 21 · 2015: 23 · 2014: 24 · 2013: 20 · 2012: 30
- FWCI
- 15.14
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS Pathogens (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- University of Cape Town
- National Institutes of Health (NIH T32)
- U.S. Public Health Service
- National Institute of Allergy and Infectious Diseases (R03AI53623, R03AI053623)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Keywords
- Aspergillus fumigatus, β-glucan, conidial germination, Dectin-1, alveolar macrophages, TNF-α, CXCL2, neutrophil recruitment, innate immunity, TLR2, MyD88, fungal pathogenesis, invasive aspergillosis, phagosome
- MeSH terms
- Dectin-1, Animals, Aspergillosis, Aspergillus fumigatus, Dendritic Cells, Intubation, Intratracheal, Lung, Membrane Proteins, Mice, Inbred BALB C, Nerve Tissue Proteins, Pneumonia, Specific Pathogen-Free Organisms, Spores, Fungal, Cytokines, Macrophages, Alveolar, Mice, Knockout, Inhalation Exposure, Lectins, C-Type, beta-Glucans, Mice
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