Abstract
The study of host–pathogen interactions has illuminated fundamental research avenues in both infection and cell biology. Zebrafish (Danio rerio) larvae are genetically tractable, optically accessible, and present a fully functional innate immune system with macrophages and neutrophils that mimic their mammalian counterparts. A wide variety of pathogenic bacteria have been investigated using zebrafish models, providing unprecedented resolution of the cellular response to infection in vivo. In this review, we illustrate how zebrafish models have contributed to our understanding of cellular microbiology by providing an in vivo platform to study host–pathogen interactions from the single cell to whole animal level. We also highlight discoveries made from zebrafish infection that hold great promise for translation into novel therapies for humans.
Highlights
The study of host–pathogen interactions has illuminated fundamental research avenues in both infection and cell biology
To highlight the breadth of zebrafish infection models currently available, we provide examples of infection using Gram-negative bacteria (Salmonella Typhimurium, Shigella flexneri, Pseudomonas aeruginosa, and Burkholderia cenocepacia), Gram-positive bacteria (Listeria monocytogenes and Staphylococcus aureus), and mycobacteria (Mycobacterium marinum, Mycobacterium abscessus, and Mycobacterium leprae)
In agreement with the breadth of roles described for autophagy in cell biology [25], and with recent literature studying bacterial autophagy using mice [26], these results indicate that autophagy needs to be carefully controlled in vivo to protect against bacterial infection
Summary
Zebrafish stable mutants can be efficiently generated with ZFNs, TALENs, or CRISPR/Cas9 These systems are based on induction of a site-specific double-stranded break, which is repaired via an error-prone non-homologous end joining mechanism. Mutants are obtained by injecting mRNA or protein for the nuclease (together with guide RNA in the case of CRISPR/Cas9) in zebrafish eggs. Generation of precise knock-in zebrafish is still challenging but can be facilitated by introducing double strand breaks at the site of interest (i.e., using TALENs or CRISPR/Cas9) [6]. Embryos manipulated using these techniques can be used for downstream functional studies, or, in the case of stable modifications, be raised to adulthood to establish a novel line.
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