Zebrafish Models of Innate Immune Responses in Infectious Diseases

Zebrafish (Danio rerio) have emerged as a pivotal vertebrate model for the dissection of innate immune mechanisms during infection. Their optical transparency in early development, genetic tractability and conservation of key immune pathways with humans enable real-time imaging of host–pathogen interactions at cellular resolution. During the first weeks post-fertilisation, zebrafish larvae possess a functional innate immune system dominated by macrophages and neutrophils, but lack adaptive immunity, providing a unique window to study primitive host responses in isolation. Transgenic reporter lines, reverse genetics and high-throughput chemical screening complement bath-immersion and microinjection infection protocols, facilitating studies of bacterial, viral and fungal agents. This platform has illuminated the dynamics of pathogen recognition, cell recruitment and cytokine signalling, and has supported the discovery of novel antivirals and immunomodulators. Practical applications span aquaculture health, emerging-virus research and preclinical evaluation of vaccines and therapeutics, underscoring the global significance of the zebrafish model in addressing infectious disease challenges.

Research from Nature Portfolio

Recent studies have harnessed zebrafish larvae to model viral peptide-induced inflammation without handling live pathogens. Synthetic fragments derived from a viral surface protein were inoculated into the swim bladder of transgenic larvae, triggering macrophage and neutrophil recruitment, elevated pro-inflammatory mediator release and histopathological changes that recapitulate aspects of human disease. Molecular dynamics and in silico docking confirmed stable peptide interactions with conserved receptors, while in vivo assays demonstrated that this approach reliably induces innate immune activation and oxidative stress. This work validates zebrafish as an effective platform for probing host inflammatory pathways and screening peptide-based immunomodulatory strategies.

Zebrafish Models of Innate Immune Responses in Infectious Diseases publication trend

The graph below shows the total number of articles in zebrafish models of innate immune responses in infectious diseases across all publications each year (not limited to Nature Index journals).

Technical terms

Innate immunity: The first line of host defence, mediated by conserved cellular and molecular mechanisms that recognise and respond rapidly to invading pathogens.

Neutrophils: Short-lived phagocytic leukocytes that migrate to infection sites to engulf and destroy microbes and release inflammatory mediators.

Macrophages: Long-lived phagocytes involved in pathogen clearance, antigen presentation and regulation of inflammation.

Transgenic line: A zebrafish strain genetically engineered to express fluorescent markers under the control of cell-type-specific promoters, enabling live imaging of immune cells.

Bath immersion: A non-invasive infection method in which pathogens suspended in water come into contact with zebrafish larvae, modelling natural exposure routes.

Interferon-stimulated genes: A set of antiviral effector genes induced by interferon signalling that inhibit viral replication and modulate immune responses.

Reverse genetics: A technique that generates pathogens with defined genetic modifications, such as fluorescent reporter insertion, to study gene function during infection.

References

1. In vivo multiscale analyses of spring viremia of carp virus (SVCV) infection: From model organism to target species. PLOS Pathogens (2024).
2. A novel insight on SARS-CoV-2 S-derived fragments in the control of the host immunity. Scientific Reports (2023).
3. Susceptibility and Permissivity of Zebrafish (Danio rerio) Larvae to Cypriniviruses. Viruses (2023).
4. Zebrafish as a model organism for virus disease research: Current status and future directions. Heliyon (2024).
5. Zebrafish as a Model for Fish Diseases in Aquaculture. Pathogens (2020).
6. Zebrafish as an alternative animal model in human and animal vaccination research. Laboratory Animal Research (2020).
7. A model 450 million years in the making: zebrafish and vertebrate immunity. Disease Models & Mechanisms (2011).
8. Pathogen Recognition and Activation of the Innate Immune Response in Zebrafish. Advances in Hematology (2012).