Dragotcytosis: Elucidation of the Mechanism for Cryptococcus neoformans Macrophage-to-Macrophage Transfer

Quigly Dragotakes1, Man Shun Fu2, Arturo Casadevall2

  • 1Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205 qdragot@jhu.edu acasade1@jhu.edu.

Insights

Cryptococcus neoformans cell-to-cell transfer between macrophages does not involve cytosol sharing. Blocking Fc and complement receptors significantly reduced transfer events, suggesting a nonlytic exocytosis followed by phagocytosis process.

Area of Science:

  • Immunology
  • Cell Biology
  • Microbiology

Background:

  • Cryptococcus neoformans is a yeast pathogen.
  • Macrophage cell-to-cell transfer is an observed phenomenon.
  • The mechanism of this transfer is currently unknown.

Purpose of the Study:

  • To investigate the mechanism of Cryptococcus neoformans cell-to-cell transfer between macrophages.
  • To determine if cytosol is transferred between donor and acceptor macrophages during this process.

Main Methods:

  • Imaging mouse macrophages labeled with CellTracker Green 5-chloromethylfluorescein diacetate.
  • Analyzing transfer events to detect cytosol sharing.
  • Blocking Fc and complement receptors to assess their role in transfer.

Main Results:

  • No transfer of cytosol was detected between donor and acceptor macrophages.
  • Blocking Fc and complement receptors significantly diminished cell-to-cell transfer events.
  • The timing of transfer events correlated with phagocytosis and exocytosis durations.

Conclusions:

  • Macrophage cell-to-cell transfer of Cryptococcus neoformans is not mediated by direct cytosol sharing.
  • The process involves nonlytic exocytosis followed by phagocytosis into a neighboring macrophage.
  • This novel mechanism is termed Dragotcytosis, representing microbial sharing between immune sentinel cells.

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