PUBLICATION
Host immune response and acute disease in a zebrafish model of Francisella pathogenesis
- Authors
- Vojtech, L.N., Sanders, G.E., Conway, C., Ostland, V., and Hansen, J.D.
- ID
- ZDB-PUB-081203-34
- Date
- 2009
- Source
- Infection and Immunity 77(2): 914-925 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Cytokines/genetics
- Cytokines/metabolism
- Disease Models, Animal
- Francisella*
- Gene Expression Regulation/immunology
- Gills/metabolism
- Gram-Negative Bacterial Infections/immunology*
- Gram-Negative Bacterial Infections/microbiology*
- Gram-Negative Bacterial Infections/pathology
- Host-Pathogen Interactions
- Immunohistochemistry
- Kidney/metabolism
- Kidney/microbiology
- Kidney/pathology
- Liver/metabolism
- Nitric Oxide Synthase Type II/genetics
- Nitric Oxide Synthase Type II/metabolism
- Spleen/metabolism
- Zebrafish
- PubMed
- 19047404 Full text @ Infect. Immun.
Citation
Vojtech, L.N., Sanders, G.E., Conway, C., Ostland, V., and Hansen, J.D. (2009) Host immune response and acute disease in a zebrafish model of Francisella pathogenesis. Infection and Immunity. 77(2):914-925.
Abstract
Members of the bacterial genus Francisella are highly virulent and infectious pathogens. New models to study Francisella pathogenesis in evolutionarily distinct species are needed to provide comparative insight as the mechanisms of host resistance and pathogen virulence are not well understood. We took advantage of the recent discovery of a novel fish-specific species of Francisella to establish a zebrafish/Francisella comparative model of pathogenesis and host immune response. Adult zebrafish were susceptible to acute Francisella-induced disease and suffered mortality in a dose-dependent manner. Using immunohistochemical analysis, we localized bacterial antigens primarily to lymphoid tissues and the liver of zebrafish following infection by intraperitoneal injection, which corresponded to regions of local cellular necrosis. Francisella sp. replicated rapidly in these tissues beginning 12 hrs post-infection and bacterial titers rose steadily, leveled off, and then decreased by 7 days post-infection. Zebrafish mounted a significant tissue-specific pro-inflammatory response to infection as measured by the upregulation of IL-1beta, IFN-gamma, and TNF-alpha mRNA beginning by 6 hrs post-infection and persisting for up to 7 days post-infection. In addition, exposure of zebrafish to heat killed bacteria demonstrated that the significant induction of IL-1beta was highly specific to live bacteria. Taken together, the pathology and immune response to acute Francisella infection in zebrafish shares many features with that in mammals, highlighting the usefulness of this new model system for addressing both general and specific questions about Francisella host-pathogen interactions via an evolutionary approach.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping