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Macrophage Cholesterol Depletion and Its Effect on the Phagocytosis of Cryptococcus neoformans
Published on: December 19, 2014
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.
Abstract:
Cryptococcus neoformans is a pathogenic yeast capable of a unique and intriguing form of cell-to-cell transfer between macrophage cells. The mechanism for cell-to-cell transfer is not understood. In this study, we imaged mouse macrophages with CellTracker Green 5-chloromethylfluorescein diacetate-labeled cytosol to ascertain whether cytosol was shared between donor and acceptor macrophages. Analysis of several transfer events detected no transfer of cytosol from donor-to-acceptor mouse macrophages. However, blocking Fc and complement receptors resulted in a major diminution of cell-to-cell transfer events. The timing of cell-to-cell transfer (11.17 min) closely approximated the sum of phagocytosis (4.18 min) and exocytosis (6.71 min) times. We propose that macrophage cell-to-cell transfer represents a nonlytic exocytosis event, followed by phagocytosis into a macrophage that is in close proximity, and name this process Dragotcytosis ("Dragot" is a Greek surname meaning "sentinel"), as it represents sharing of a microbe between two sentinel cells of the innate immune system.
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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