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Updated: Apr 28, 2026
Infection of Zebrafish Larvae with Aspergillus Spores for Analysis of Host-Pathogen Interactions
Published on: May 16, 2020
Distinct innate immune phagocyte responses to Aspergillus fumigatus conidia and hyphae in zebrafish larvae
Benjamin P Knox1, Qing Deng2, Mary Rood3
1Microbiology Doctoral Training Program, University of Wisconsin-Madison, Madison, Wisconsin, USA Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Abstract:
Aspergillus fumigatus is the most common filamentous fungal pathogen of immunocompromised hosts, resulting in invasive aspergillosis (IA) and high mortality rates. Innate immunity is known to be the predominant host defense against A. fumigatus; however, innate phagocyte responses to A. fumigatus in an intact host and their contributions to host survival remain unclear. Here, we describe a larval zebrafish A. fumigatus infection model amenable to real-time imaging of host-fungal interactions in live animals. Following infection with A. fumigatus, innate phagocyte populations exhibit clear preferences for different fungal morphologies: macrophages rapidly phagocytose conidia and form aggregates around hyphae, while the neutrophil response is dependent upon the presence of hyphae. Depletion of macrophages rendered host larvae susceptible to invasive disease. Moreover, a zebrafish model of human leukocyte adhesion deficiency with impaired neutrophil function also resulted in invasive disease and impaired host survival. In contrast, macrophage-deficient but not neutrophil-deficient larvae exhibited attenuated disease following challenge with a less virulent (ΔlaeA) strain of A. fumigatus, which has defects in secondary metabolite production. Taking these results together, we have established a new vertebrate model for studying innate immune responses to A. fumigatus that reveals distinct roles for neutrophils and macrophages in mediating host defense against IA.
Insights
This study reveals distinct roles for macrophages and neutrophils in defending against Aspergillus fumigatus (IA). Zebrafish models show macrophages are crucial for early defense, while neutrophils target fungal hyphae, impacting host survival in invasive aspergillosis.
Area of Science:
- Mycology
- Immunology
- Zebrafish models
Background:
- Aspergillus fumigatus is a leading cause of invasive aspergillosis (IA) in immunocompromised individuals.
- Innate immune responses, particularly phagocytes, are critical for controlling fungal infections.
- The specific roles of macrophages and neutrophils in host defense against A. fumigatus remain incompletely understood.
Purpose of the Study:
- To investigate the distinct roles of innate phagocytes (macrophages and neutrophils) in host defense against Aspergillus fumigatus.
- To establish and utilize a larval zebrafish model for real-time imaging of host-fungal interactions.
- To determine the contribution of different phagocyte populations to host survival during invasive aspergillosis.
Main Methods:
- Larval zebrafish infection model with Aspergillus fumigatus.
- Real-time imaging of host-fungal interactions.
- Phagocyte depletion (macrophages and neutrophils) and functional impairment (leukocyte adhesion deficiency model).
- Challenge with virulent and less virulent (ΔlaeA) A. fumigatus strains.
Main Results:
- Macrophages preferentially phagocytosed conidia and aggregated around hyphae; neutrophils responded to hyphae.
- Macrophage depletion led to susceptibility to invasive disease.
- Impaired neutrophil function resulted in invasive disease and reduced host survival.
- Macrophage-deficient larvae showed attenuated disease against a less virulent fungal strain.
Conclusions:
- Established a novel vertebrate model for studying innate immunity against Aspergillus fumigatus.
- Demonstrated distinct and complementary roles for macrophages and neutrophils in controlling invasive aspergillosis.
- Highlighted the critical importance of macrophage phagocytosis and neutrophil response to hyphae for host survival.
