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

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. Here we imaged macrophages with CellTracker Green CMFDA-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 macrophages. However, blocking Fc and complement receptors resulted in a major diminution of cell-to-cell transfer events. The timing 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 non-lytic 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. Microarrays were used to assess whether incubation of Bone Marrow-derived macrophages (BMDMs) with receptor blocking antibodies had an effect on their transcriptional profiles. BMDMs incubated with or without the Fc receptor blocking antibody were processed in triplicate for each condition.