Essential Role for Neutrophils but not Alveolar Macrophages at Early Time Points following Aspergillus fumigatus Infection

Mircescu, Monica M.; Lipuma, Lauren; van Rooijen, Nico; Pamer, Eric G.; Hohl, Tobias M.

doi:10.1086/600380

Cited by 216Antifungal resistance and susceptibilityNeutrophil, Myeloperoxidase and Oxidative MechanismsFungal and yeast genetics research

Essential Role for Neutrophils but not Alveolar Macrophages at Early Time Points following Aspergillus fumigatus Infection

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Mircescu, Monica M., Lipuma, Lauren, van Rooijen, Nico, Pamer, Eric G., Hohl, Tobias M.·2009·The Journal of Infectious Diseases

DOI 10.1086/600380PMC PMC2745295

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Abstract

Alveolar macrophages and neutrophils mediate innate immune defense against the opportunistic fungal pathogen Aspergillus fumigatus and are believed to be essential for host survival following inhalation of fungal spores (conidia). Although alveolar macrophages are postulated to kill inhaled conidia and neutrophils are believed to act against hyphae, the relative contribution of alveolar macrophages and neutrophils to early defense against A. fumigatus remain incompletely defined. To more precisely characterize the contributions of alveolar macrophages and neutrophils in antifungal host defense, we selectively depleted each cell population at different times following pulmonary challenge with conidia. Mice depleted of alveolar macrophages prior to pulmonary A. fumigatus infection recruited neutrophils normally and restricted hyphal tissue invasion. In contrast, neutrophil depletion prior to or within 3 h after infection was associated with high mortality. Neutrophil depletion at later time points, however, was associated with nearly normal survival rates. Our studies suggest that neutrophils, but not alveolar macrophages, provide essential anticonidial defense and that a brief period of influx into the respiratory tree is sufficient to prevent conidial germination and invasive disease.

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Neutrophil depletion within 3 h after Aspergillus challenge in immunocompetent mice results in lethal infections.
“Notably, neutrophil depletion within 3 h after Aspergillus challenge in immunocompetent mice results in lethal infections (275).”
From Aspergillus fumigatus and Aspergillosis in 2019 (2019) · cites this paper as [275]

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Postinfluenza Environment Reduces Aspergillus fumigatus Conidium Clearance and Facilitates Invasive Aspergillosis In Vivo
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MDA5 Is an Essential Sensor of a Pathogen-Associated Molecular Pattern Associated with Vitality That Is Necessary for Host Resistance against Aspergillus fumigatus
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PKC-δ activation in neutrophils promotes fungal clearance
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Neutrophils but not Alveolar Macrophages are Essential at Early Time Points Following Aspergillus Infection
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Authors: Mircescu, M. M., Lipuma, L., van Rooijen, N., Pamer, E. G., & Hohl, T. M.
Affiliations: Memorial Sloan Kettering Cancer Center (US)
ORCID: Lipuma, Lauren
Pamer, Eric G.
Hohl, Tobias M.
Venue: The Journal of Infectious Diseases
Publisher: Oxford University Press (OUP)
Published: 2009-08-15
Volume: 200
Issue: 4
Pages: 647-656
ISSN: 0022-1899 (ISSN-L)
1537-6613
DOI: 10.1086/600380
PMC: PMC2745295
OpenAlex: W2160702475
Cited by: 216
References: 49
Citations by year: 2026: 4 · 2025: 10 · 2024: 14 · 2023: 10 · 2022: 17 · 2021: 9 · 2020: 15 · 2019: 13 · 2018: 8 · 2017: 18 · 2016: 13 · 2015: 19 · 2014: 15 · 2013: 9 · 2012: 9
FWCI: 9.63
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: The Journal of Infectious Diseases (publishedVersion)
PubMed (publishedVersion)
Pure Amsterdam UMC (publishedVersion)
Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Digital Academic REpository of VU University Amsterdam (Vrije Universiteit Amsterdam) (submittedVersion)
Data Archiving and Networked Services (DANS) (submittedVersion)
Funders: National Institute of Allergy and Infectious Diseases (T32AI055409, R01AI080619, K08AI071998, R01AI067359)
Topics: Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
Keywords: Aspergillus fumigatus, neutrophils, alveolar macrophages, pulmonary aspergillosis, neutrophil depletion, conidial germination, invasive aspergillosis
MeSH terms: Animals, Aspergillus fumigatus, Lung, Mice, Inbred C57BL, Neutrophils, Time Factors, Macrophages, Alveolar, Mice, Pulmonary Aspergillosis

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Essential Role for Neutrophils but not Alveolar Macrophages at Early Time Points following Aspergillus fumigatus Infection

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