PUBLICATION
Distinct Innate Immune Phagocyte Responses to Aspergillus fumigatus Conidia and Hyphae in Zebrafish Larvae
- Authors
- Knox, B.P., Deng, Q., Rood, M., Eickhoff, J.C., Keller, N.P., Huttenlocher, A.
- ID
- ZDB-PUB-140601-3
- Date
- 2014
- Source
- Eukaryotic Cell 13(10): 1266-77 (Journal)
- Registered Authors
- Huttenlocher, Anna
- Keywords
- none
- MeSH Terms
-
- Animals
- Aspergillosis/immunology
- Aspergillosis/microbiology
- Aspergillus fumigatus/immunology
- Aspergillus fumigatus/pathogenicity
- Host-Parasite Interactions/immunology*
- Humans
- Hyphae/immunology
- Hyphae/pathogenicity
- Immunity, Innate*
- Larva/immunology
- Larva/microbiology
- Macrophages/immunology
- Phagocytes/immunology*
- Phagocytosis
- Spores, Fungal/immunology
- Spores, Fungal/pathogenicity
- Zebrafish/immunology*
- Zebrafish/microbiology
- PubMed
- 24879123 Full text @ Eukaryot. Cell
Citation
Knox, B.P., Deng, Q., Rood, M., Eickhoff, J.C., Keller, N.P., Huttenlocher, A. (2014) Distinct Innate Immune Phagocyte Responses to Aspergillus fumigatus Conidia and Hyphae in Zebrafish Larvae. Eukaryotic Cell. 13(10):1266-77.
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 in an intact host to A. fumigatus 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 strain of A. fumigatus, ΔlaeA, which has defects in secondary metabolite production. Taken 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping