Utilization of zebrafish for intravital study of eukaryotic pathogen–host interactions

Gratacap, Remi L.; Wheeler, Robert T.

doi:10.1016/j.dci.2014.01.020

Cited by 37 publications

(28 citation statements)

References 107 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The larval zebrafish offers a unique vertebrate model for studying bacterial, viral, and fungal infections (40)(41)(42). This transparent host allows the simultaneous longitudinal study of host and pathogen interactions intravitally, enabling us to ask questions we cannot investigate in vitro or in murine models.…”

mentioning

confidence: 99%

Yeast and Filaments Have Specialized, Independent Activities in a Zebrafish Model of Candida albicans Infection

et al. 2018

Self Cite

View full text Add to dashboard Cite

dimorphism is a crucial virulence factor during invasive candidiasis infections, which claim the lives of nearly one-half of those afflicted. It has long been believed that filaments drive tissue invasion and yeast mediate bloodstream dissemination, but observation of these activities during infection has been prevented by technical limitations. We used a transparent zebrafish infection model to more comprehensively analyze how utilizes shape to disseminate and invade. This model facilitated the use of diverse, complementary strategies to manipulate shape, allowing us to monitor dissemination, invasion, and pathogenesis via intravital imaging of individual fungal cells throughout the host. To control fungal cell shape, we employed three different strategies: gene deletion (Δ/ΔΔ/Δ, Δ/Δ), overexpression of master regulators ( or ), and modulation of infection temperature (21°C, 28°C, 33°C). The effects of these orthogonal manipulations were consistent, support the proposed specialized roles of yeast in dissemination and filaments in tissue invasion and pathogenesis, and indicate conserved mechanisms in zebrafish. To test if either morphotype changes the effectiveness of the other, we infected fish with a known mix of shape-locked strains. Surprisingly, mixed infections were associated with additive, but not synergistic, filament invasion and yeast dissemination. These findings provide the most complete view of morphotype-function relationships for to date, revealing independent roles of yeast and filaments during disseminated candidiasis.

show abstract

mentioning

confidence: 99%

Yeast and Filaments Have Specialized, Independent Activities in a Zebrafish Model of Candida albicans Infection

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…The zebrafish larva is a simplified model organism that combines the advantages of high-resolution imaging available in vitro with an examination of infection dynamics in vivo with a vertebrate immune system and has been useful in studying bacterial, viral, fungal, and parasitic infections (25,26). We recently developed the first microinjection mucosal infection model in the zebrafish larva, and it has been used to study sterile inflammation and infection with both viral and fungal pathogens (27)(28)(29).…”

mentioning

confidence: 99%

Control of Mucosal Candidiasis in the Zebrafish Swim Bladder Depends on Neutrophils That Block Filament Invasion and Drive Extracellular-Trap Production

2017

Self Cite

View full text Add to dashboard Cite

Candida albicans is a ubiquitous mucosal commensal that is normally prevented from causing acute or chronic invasive disease. Neutrophils contribute to protection in oral infection but exacerbate vulvovaginal candidiasis. To dissect the role of neutrophils during mucosal candidiasis, we took advantage of a new, transparent zebrafish swim bladder infection model. Intravital microscopic tracking of individual animals revealed that the blocking of neutrophil recruitment leads to rapid mortality in this model through faster disease progression. Conversely, artificial recruitment of neutrophils during early infection reduces disease pressure. Noninvasive longitudinal tracking showed that mortality is a consequence of C. albicans breaching the epithelial barrier and invading surrounding tissues. Accordingly, we found that a hyperfilamentous C. albicans strain breaches the epithelial barrier more frequently and causes mortality in immunocompetent zebrafish. A lack of neutrophils at the infection site is associated with less fungusassociated extracellular DNA and less damage to fungal filaments, suggesting that neutrophil extracellular traps help to protect the epithelial barrier from C. albicans breach. We propose a homeostatic model where C. albicans disease pressure is balanced by neutrophil-mediated damage of fungi, maintaining this organism as a commensal while minimizing the risk of damage to host tissue. The unequaled ability to dissect infection dynamics at a high spatiotemporal resolution makes this zebrafish model a unique tool for understanding mucosal host-pathogen interactions.KEYWORDS Candida albicans, mucosal immunity, neutrophils, zebrafish C andida albicans is the most successful commensal fungus at causing opportunistic mucosal and invasive infections (1, 2). The opportunistic nature of C. albicans mucosal infection suggests that there is a constantly challenged impasse between our immune defenses and C. albicans virulence factors (3, 4). Chronic mucocutaneous candidiasis (CMC) is associated with inborn errors of adaptive immune pathways, especially Th17 immunity (5). However, acute oropharyngeal candidiasis (OPC) is more common in neutropenic patients and can result from a multitude of immunesuppressive treatments that affect both innate and adaptive immunity, such as radiation/chemotherapy and corticosteroid or antibiotic use (6, 7).Experimental work in murine models of OPC suggests that C. albicans is kept at bay in mucosal tissues through the action of epithelial cells, neutrophils, and macrophages (8). To protect from mucosal invasion in OPC, neutrophils must be present in the blood, be recruited to the site of infection, and possess a fully functional antimicrobial arsenal (9-12). Neutrophils attack both the yeast and filamentous forms of C. albicans and are associated with vulvovaginal candidiasis (13-15). Counterintuitively, because symptomatic infection is more closely associated with high neutrophil numbers than with the fungal burden, it is believed that neutrophils do more to cause...

show abstract

“…Regarding infectious diseases, some 30 different bacterial pathogens have been studied using the zebrafish model (Meijer & Spaink, 2011; Torraca, Masud, Spaink, & Meijer, 2014; Torraca & Mostowy, 2018). The zebrafish is also being used as a model for viral and parasitic diseases, including those that infect humans (Crim & Riley, 2012; Gratacap & Wheeler, 2014). Holding zebrafish at elevated temperatures enables them to be infected with human pathogens (Brudal et al, 2014; Meijer, 2016; Stones et al, 2017; Tenor, Oehlers, Yang, Tobin, & Perfect, 2015).…”

Section: Introductionmentioning

confidence: 99%

Review of diseases and health management in zebrafish Danio rerio (Hamilton 1822) in research facilities

Kent

Sanders

Spagnoli

et al. 2020

Journal of Fish Diseases

View full text Add to dashboard Cite

The use of zebrafish (Danio rerio) in biomedical research has expanded at a tremendous rate over the last two decades. Along with increases in laboratories using this model, we are discovering new and important diseases. We review here the important pathogens and diseases based on some 20 years of research and findings from our diagnostic service at the NIH-funded Zebrafish International Resource Center. Descriptions of the present status of biosecurity programmes and diagnostic and treatment approaches are included. The most common and important diseases and pathogens are two parasites, Pseudoloma neurophilia and Pseudocapillaria tomentosa, and mycobacteriosis caused by Mycobacterium chelonae, M. marinum and M. haemophilum. Less common but deadly diseases are caused by Edwardsiella ictaluri and infectious spleen and kidney necrosis virus (ISKNV). Hepatic megalocytosis and eggassociated inflammation and fibroplasia are common, apparently non-infectious, in zebrafish laboratories. Water quality diseases include supersaturation and nephrocalcinosis. Common neoplasms are spindle cell sarcomas, ultimobranchial tumours, spermatocytic seminomas and a small-cell carcinoma that is caused by a transmissible agent. Despite the clear biosecurity risk, researchers continue to use fish from pet stores, and here, we document two novel coccidia associated with significant lesions in zebrafish from one of these stores. K E Y W O R D S biosecurity, Danio rerio, diagnostics, fish diseases, treatment

show abstract

Utilization of zebrafish for intravital study of eukaryotic pathogen–host interactions

Cited by 37 publications

References 107 publications

Yeast and Filaments Have Specialized, Independent Activities in a Zebrafish Model of Candida albicans Infection

Yeast and Filaments Have Specialized, Independent Activities in a Zebrafish Model of Candida albicans Infection

Control of Mucosal Candidiasis in the Zebrafish Swim Bladder Depends on Neutrophils That Block Filament Invasion and Drive Extracellular-Trap Production

Review of diseases and health management in zebrafish Danio rerio (Hamilton 1822) in research facilities

Contact Info

Product

Resources

About