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Updated: Apr 3, 2026
Modeling Mucosal Candidiasis in Larval Zebrafish by Swimbladder Injection
Published on: November 27, 2014
A zebrafish larval model reveals early tissue-specific innate immune responses to Mucor circinelloides
Kerstin Voelz1, Remi L Gratacap2, Robert T Wheeler2
1Institute of Microbiology and Infection, School of Biosciences, University of Birmingham B15 2TT, UK Department of Molecular and Biomedical Sciences, University of Maine, Orono, ME 04469, USA National Institute of Health Research Surgical Reconstruction and Microbiology Research Centre, Queen Elizabeth Hospital, Birmingham B15 2TH, UK k.voelz@bham.ac.uk.
Abstract:
Mucormycosis is an emerging fungal infection that is clinically difficult to manage, with increasing incidence and extremely high mortality rates. Individuals with diabetes, suppressed immunity or traumatic injury are at increased risk of developing disease. These individuals often present with defects in phagocytic effector cell function. Research using mammalian models and phagocytic effector cell lines has attempted to decipher the importance of the innate immune system in host defence against mucormycosis. However, these model systems have not been satisfactory for direct analysis of the interaction between innate immune effector cells and infectious sporangiospores in vivo. Here, we report the first real-time in vivo analysis of the early innate immune response to mucormycete infection using a whole-animal zebrafish larval model system. We identified differential host susceptibility, dependent on the site of infection (hindbrain ventricle and swim bladder), as well as differential functions of the two major phagocyte effector cell types in response to viable and non-viable spores. Larval susceptibility to mucormycete spore infection was increased upon immunosuppressant treatment. We showed for the first time that macrophages and neutrophils were readily recruited in vivo to the site of infection in an intact host and that spore phagocytosis can be observed in real-time in vivo. While exploring innate immune effector recruitment dynamics, we discovered the formation of phagocyte clusters in response to fungal spores that potentially play a role in fungal spore dissemination. Spores failed to activate pro-inflammatory gene expression by 6 h post-infection in both infection models. After 24 h, induction of a pro-inflammatory response was observed only in hindbrain ventricle infections. Only a weak pro-inflammatory response was initiated after spore injection into the swim bladder during the same time frame. In the future, the zebrafish larva as a live whole-animal model system will contribute greatly to the study of molecular mechanisms involved in the interaction of the host innate immune system with fungal spores during mucormycosis.
Insights
This study introduces a zebrafish larva model for real-time analysis of mucormycosis, revealing differential immune cell responses and host susceptibility to fungal spores in vivo. The findings advance understanding of innate immunity against this dangerous infection.
Area of Science:
- Mycology
- Immunology
- Zebrafish models
Background:
- Mucormycosis is a severe fungal infection with high mortality, often affecting immunocompromised individuals.
- Existing mammalian models are limited for studying early host-pathogen interactions in vivo.
- Understanding the innate immune response is crucial for managing mucormycosis.
Purpose of the Study:
- To develop and utilize a novel whole-animal zebrafish larva model for real-time in vivo analysis of early innate immune responses to mucormycete infection.
- To investigate differential host susceptibility and phagocyte effector cell functions during mucormycosis.
- To elucidate the dynamics of immune cell recruitment and inflammatory responses.
Main Methods:
- Utilized a zebrafish larval model for whole-animal, real-time in vivo imaging of mucormycete spore infection.
- Analyzed differential host susceptibility based on infection site (hindbrain ventricle, swim bladder).
- Observed and characterized macrophage and neutrophil recruitment, phagocytosis, and inflammatory gene expression.
Main Results:
- Identified differential host susceptibility and distinct roles for macrophages and neutrophils in response to fungal spores.
- Demonstrated real-time in vivo visualization of phagocyte recruitment and spore phagocytosis.
- Observed formation of phagocyte clusters and delayed/site-specific pro-inflammatory gene induction.
Conclusions:
- The zebrafish larva model provides a powerful platform for studying mucormycosis pathogenesis and host-innate immune interactions in real-time.
- Findings highlight the complex interplay between immune cells, fungal spores, and infection site in determining disease outcome.
- This model system holds promise for future research into the molecular mechanisms of mucormycosis.
