Mycobacterial Infection Dynamics in Zebrafish Models

Zebrafish (Danio rerio) have emerged as a powerful vertebrate model for dissecting the complex interplay between mycobacteria and the host innate immune system. Optical transparency and genetic tractability permit real-time imaging of pathogen entry, phagocyte recruitment and granuloma assembly at single-cell resolution. Upon inoculation with Mycobacterium marinum, zebrafish larvae mount rapid neutrophil and macrophage responses that attempt to contain bacteria via phagocytosis and production of reactive nitrogen species. In many instances macrophages coalesce into organised granulomas that both restrain bacterial growth and create niches for persisting bacilli. Detailed analyses have revealed how bacterial virulence determinants manipulate host signalling circuits to promote cell necrosis, facilitate escape from tissue-resident macrophages and recruit permissive monocytes for dissemination. Genetic and pharmacological perturbations in zebrafish have identified host regulators of nitric oxide synthesis, inflammatory cytokine cascades and autophagy pathways that modulate infection outcomes. Furthermore, the model has accelerated the evaluation of novel antimicrobial agents, delivery systems and host-directed therapies by allowing simultaneous assessment of efficacy, toxicity and pharmacokinetics in vivo. Collectively, zebrafish studies have transformed our understanding of granuloma biology, cell death mechanisms and the cellular choreography that underpins both containment and spread of mycobacterial infection, with clear implications for human tuberculosis research and drug development.

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Mycobacterial Infection Dynamics in Zebrafish Models publication trend

The graph below shows the total number of articles in mycobacterial infection dynamics in zebrafish models across all publications each year (not limited to Nature Index journals).

Technical terms

Granuloma: An organised aggregate of immune cells, primarily macrophages, that forms around persistent pathogens to contain infection.

Macrophage: A phagocytic immune cell that engulfs pathogens, presents antigens and orchestrates inflammatory responses.

Phagocytosis: The process by which cells internalise microorganisms or particles into membrane-bound vesicles for degradation.

Mycobacterium marinum: A close relative of Mycobacterium tuberculosis that causes tuberculosis-like disease in fish and is used as a zebrafish infection model.

Inducible nitric oxide synthase (iNOS): An enzyme expressed in activated macrophages that generates nitric oxide, a microbicidal and signalling molecule.

References

1. Tribbles1 is host protective during in vivo mycobacterial infection. eLife (2024).
2. Specificity of the innate immune responses to different classes of non-tuberculous mycobacteria. Frontiers in Immunology (2023).
3. Subcellular localization and therapeutic efficacy of polymeric micellar nanoparticles encapsulating bedaquiline for tuberculosis treatment in zebrafish. Biomaterials Science (2023).