PUBLICATION
Cryptococcus neoformans Intracellular Proliferation and Capsule Size Determines Early Macrophage Control of Infection
- Authors
- Bojarczuk, A., Miller, K.A., Hotham, R., Lewis, A., Ogryzko, N.V., Kamuyango, A.A., Frost, H., Gibson, R.H., Stillman, E., May, R.C., Renshaw, S.A., Johnston, S.A.
- ID
- ZDB-PUB-160219-12
- Date
- 2016
- Source
- Scientific Reports 6: 21489 (Journal)
- Registered Authors
- Bojarczuk, Aleks, Ogryzko, Nikolay, Renshaw, Steve A.
- Keywords
- Fungal infection, Fungal pathogenesis, Imaging the immune system
- MeSH Terms
-
- Animals
- Cell Proliferation*
- Cryptococcosis/metabolism*
- Cryptococcosis/pathology
- Cryptococcus neoformans/metabolism*
- Fish Diseases/metabolism*
- Fish Diseases/microbiology
- Macrophages/metabolism*
- Macrophages/microbiology
- Organisms, Genetically Modified/metabolism
- Zebrafish/metabolism*
- Zebrafish/microbiology
- PubMed
- 26887656 Full text @ Sci. Rep.
Citation
Bojarczuk, A., Miller, K.A., Hotham, R., Lewis, A., Ogryzko, N.V., Kamuyango, A.A., Frost, H., Gibson, R.H., Stillman, E., May, R.C., Renshaw, S.A., Johnston, S.A. (2016) Cryptococcus neoformans Intracellular Proliferation and Capsule Size Determines Early Macrophage Control of Infection. Scientific Reports. 6:21489.
Abstract
Cryptococcus neoformans is a significant fungal pathogen of immunocompromised patients. Many questions remain regarding the function of macrophages in normal clearance of cryptococcal infection and the defects present in uncontrolled cryptococcosis. Two current limitations are: 1) The difficulties in interpreting studies using isolated macrophages in the context of the progression of infection, and 2) The use of high resolution imaging in understanding immune cell behavior during animal infection. Here we describe a high-content imaging method in a zebrafish model of cryptococcosis that permits the detailed analysis of macrophage interactions with C. neoformans during infection. Using this approach we demonstrate that, while macrophages are critical for control of C. neoformans, a failure of macrophage response is not the limiting defect in fatal infections. We find phagocytosis is restrained very early in infection and that increases in cryptococcal number are driven by intracellular proliferation. We show that macrophages preferentially phagocytose cryptococci with smaller polysaccharide capsules and that capsule size is greatly increased over twenty-four hours of infection, a change that is sufficient to severely limit further phagocytosis. Thus, high-content imaging of cryptococcal infection in vivo demonstrates how very early interactions between macrophages and cryptococci are critical in the outcome of cryptococcosis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping