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Dendritic cells restrict the transformation of Histoplasma capsulatum conidia into yeasts

Simon L Newman1, Wendy Lemen, Alan G Smulian

  • 1Division of Infectious Diseases, Department of Medicine, University of Cincinnati College of Medicine, PO Box 670560, Cincinnati, OH 45267-0560, USA. newmansl@ucmail.uc.edu

Medical Mycology
|November 3, 2010
PubMed

Insights

Histoplasma capsulatum conidia transform into yeast within macrophages (MΦ) rapidly, but transformation is delayed in dendritic cells (DC). This study quantifies the fungal transformation process in these key immune cells.

Area of Science:

  • Mycology
  • Immunology
  • Cell Biology

Background:

  • Histoplasma capsulatum infections originate from inhaled mold conidia.
  • Fungal transformation from conidia to yeast is crucial for pathogenesis.
  • Macrophages (MΦ) and dendritic cells (DC) are key immune cells involved in host defense.

Purpose of the Study:

  • To quantify the time course of Histoplasma capsulatum conidia transformation into yeast-like cells within MΦ and DC.
  • To compare the transformation efficiency and kinetics in MΦ versus DC.
  • To assess the impact of fungal transformation on host cell viability.

Main Methods:

  • Infection of human and murine MΦ and DC with surface-labeled or GFP-expressing Histoplasma capsulatum conidia.
  • Quantification of intracellular conidia and yeast using phase-contrast and fluorescent microscopy.
  • Measurement of conidia transformation via ³H-leucine incorporation.
  • Monitoring of host cell monolayer integrity over time.

Main Results:

  • Yeast-like cells appeared by day 3 post-infection in MΦ, mirroring transformation in culture medium.
  • Transformation was significantly restricted in human and murine DC, with yeasts appearing by day 5.
  • MΦ monolayers were destroyed by day 6-7, while DC monolayers remained intact.

Conclusions:

  • Histoplasma capsulatum conidia transform efficiently in MΦ, regardless of phagocytosis.
  • Transformation is significantly restricted within DC, suggesting a differential role in host-pathogen interaction.
  • DC may play a distinct role in controlling fungal burden compared to MΦ.

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