Cited by 428Antifungal resistance and susceptibilityImmune Response and InflammationFungal and yeast genetics research

Aspergillus fumigatus Triggers Inflammatory Responses by Stage-Specific β-Glucan Display

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Hohl, Tobias M, Van Epps, Heather L., Rivera, Amariliz, Morgan, Laura A, Chen, Patrick L, Feldmesser, Marta, Pamer, Eric G·2005·PLoS Pathogens

Abstract

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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Crossref · 10.1371/journal.ppat.0010030

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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.

    “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]

  • The discovery of selective activation of Dectin-1/Syk signaling during germination of Aspergillus conidia due to stage-specific surface exposure of β-glucan and the ability of PRR to regulate phagosome maturation provided the conceptual framework of PAMPs masking as a mechanism employed by fungi to escape macrophage killing.

    “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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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
Published
2005-11-18
Volume
1
Issue
3
Pages
e30
ISSN
  • 1553-7366 (ISSN-L)
  • 1553-7374
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
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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