Protection and pathology in TB: learning from the zebrafish model

Area of Science:

• Infectious Diseases
• Immunology
• Animal Models

Background:

• Zebrafish are increasingly utilized as a model organism for studying tuberculosis (TB).
• Mycobacterium marinum, a natural zebrafish pathogen, shares key virulence factors with Mycobacterium tuberculosis, the human TB pathogen.
• Zebrafish models allow for the study of both acute and chronic TB infections, including latent infection.

Purpose of the Study:

• To highlight the utility of zebrafish models in understanding tuberculosis pathogenesis.
• To showcase how zebrafish models facilitate the visualization and study of granuloma formation and immune responses.
• To emphasize the application of zebrafish models in exploring novel host-directed therapies for TB.

Main Methods:

• Infection of adult zebrafish with Mycobacterium marinum to study adaptive immunity and granuloma formation.
• Infection of zebrafish embryos and larvae to visualize early granuloma development using innate immunity.
• Microinjection of mycobacteria into various tissues to induce localized or systemic infections.
• Non-invasive imaging techniques to observe phagocyte recruitment, granuloma vascularization, and dissemination.

Main Results:

• Zebrafish models recapitulate key aspects of TB, including caseating granuloma formation and latent infection.
• Visualization of early granuloma development in transparent zebrafish embryos and larvae.
• Insights into mycobacteria-driven mechanisms of granuloma formation, inflammation, and macrophage cell death.
• Demonstration of the host-protective role of autophagy in TB infection.

Conclusions:

• Zebrafish models are valuable tools for dissecting TB pathogenesis and immune responses.
• These models enable the study of granuloma dynamics and host-pathogen interactions in real-time.
• Zebrafish research contributes to the development of new host-directed adjunctive therapies for tuberculosis.