ZFIN ID: ZDB-PUB-110523-10
Live imaging of disseminated candidiasis in zebrafish reveals role of phagocyte oxidase in limiting filamentous growth
Brothers, K., Newman, Z., and Wheeler, R.
Date: 2011
Source: Eukaryotic Cell   10(7): 932-44 (Journal)
Registered Authors: Wheeler, Robert
Keywords: none
MeSH Terms:
  • Animals
  • Candida albicans*/growth & development
  • Candida albicans*/pathogenicity
  • Candidiasis/immunology
  • Candidiasis/pathology*
  • Cytoskeleton/metabolism
  • Gene Knockout Techniques
  • Host-Pathogen Interactions*
  • Macrophages/microbiology
  • NADPH Oxidases/metabolism*
  • Neutrophils/microbiology
  • Oxidative Stress
  • Phagocytes
  • Reactive Oxygen Species
  • Virulence
  • Zebrafish/growth & development
  • Zebrafish/metabolism*
  • Zebrafish/microbiology*
PubMed: 21551247 Full text @ Eukaryot. Cell
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ABSTRACT
Candida albicans is a human commensal and clinically important fungal pathogen that grows as both yeast and hyphae during human infection. Although Candida can cause cutaneous and mucosal disease, systemic infections cause the greatest mortality in hospitals. Candidemia occurs primarily in immunocompromised patients, for whom the innate immune system plays a paramount role in immunity. We have developed a novel transparent vertebrate model of candidemia to probe the molecular nature of Candida-innate immune interactions in an intact host. Our zebrafish infection model results in lethal disseminated disease that shares important traits with disseminated candidiasis in mammals: dimorphic fungal growth, dependence on hyphal growth for virulence, and dependence on the phagocyte NADPH oxidase for immunity. Dual imaging of fluorescently marked immune cells and fungi revealed that phagocytosed yeast can remain viable and even divide within macrophages without germinating. Similarly, although we observed apparently killed yeast within neutrophils, most yeast within these innate immune cells were viable. Exploiting this model, we combined intravital imaging with gene knockdown to show for the first time that NADPH oxidase is required for regulation of C. albicans filamentation in vivo. The transparent and easily manipulated larval zebrafish model promises to provide a unique tool to dissect the molecular basis for phagocyte NADPH oxidase-mediated limitation of filamentous growth in vivo.
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