PUBLICATION
Macrophages inhibit Aspergillus fumigatus germination and neutrophil-mediated fungal killing
- Authors
- Rosowski, E.E., Raffa, N., Knox, B.P., Golenberg, N., Keller, N.P., Huttenlocher, A.
- ID
- ZDB-PUB-180803-8
- Date
- 2018
- Source
- PLoS pathogens 14: e1007229 (Journal)
- Registered Authors
- Huttenlocher, Anna, Rosowski, Emily E.
- Keywords
- none
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Aspergillosis/immunology
- Aspergillosis/microbiology
- Aspergillus fumigatus/genetics
- Aspergillus fumigatus/immunology*
- Aspergillus fumigatus/physiology*
- Cytotoxicity, Immunologic*
- Larva
- Macrophages/physiology*
- Neutrophils/physiology*
- Organisms, Genetically Modified
- Phagocytosis/immunology
- Spores, Fungal/genetics
- Spores, Fungal/immunology*
- Zebrafish/embryology
- Zebrafish/growth & development
- Zebrafish/immunology
- PubMed
- 30071103 Full text @ PLoS Pathog.
Citation
Rosowski, E.E., Raffa, N., Knox, B.P., Golenberg, N., Keller, N.P., Huttenlocher, A. (2018) Macrophages inhibit Aspergillus fumigatus germination and neutrophil-mediated fungal killing. PLoS pathogens. 14:e1007229.
Abstract
In immunocompromised individuals, Aspergillus fumigatus causes invasive fungal disease that is often difficult to treat. Exactly how immune mechanisms control A. fumigatus in immunocompetent individuals remains unclear. Here, we use transparent zebrafish larvae to visualize and quantify neutrophil and macrophage behaviors in response to different A. fumigatus strains. We find that macrophages form dense clusters around spores, establishing a protective niche for fungal survival. Macrophages exert these protective effects by inhibiting fungal germination, thereby inhibiting subsequent neutrophil recruitment and neutrophil-mediated killing. Germination directly drives fungal clearance as faster-growing CEA10-derived strains are killed better in vivo than slower-growing Af293-derived strains. Additionally, a CEA10 pyrG-deficient strain with impaired germination is cleared less effectively by neutrophils. Host inflammatory activation through Myd88 is required for killing of a CEA10-derived strain but not sufficient for killing of an Af293-derived strain, further demonstrating the role of fungal-intrinsic differences in the ability of a host to clear an infection. Altogether, we describe a new role for macrophages in the persistence of A. fumigatus and highlight the ability of different A. fumigatus strains to adopt diverse modes of virulence.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping