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. 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.

Unravelling the interactions of the environmental hostAcanthamoeba castellaniiwith fungi through the recognition by mannose‐binding proteins

“…The extrusion (vomocytosis) phenomenon, already described for C. neoformans – Ac , was also observed for all the instances tested at distinct rates. However, our conditions do not distinguish whether these events are regurgitation of ingested yeasts by amoeba or a fungal‐triggered exocytosis event as recently described for the C. neoformans –macrophage interaction (Dragotakes, Fu, & Casadevall, ). The interaction of the dimorphic fungus P. brasiliensis and Ac has not been described previously; however, Ac could also work as a potential host for the filamentous environmental phase or when returning from pathogenic phase to the environment (Arantes, Theodoro, Teixeira Mde, Bosco Sde, & Bagagli, ; Boyce & Andrianopoulos, ).…”

The mouse lung early cellular innate immune response is not sufficient to control fungal infection with Cryptococcus neoformans

“…There was a complete lack of a host or pathogen phenotype in the presence of antibody opsonin. This contradicts many in vitro cryptococcal studies, where 18B7 antibody is said to be required for phagocytosis by macrophage and macrophage like cell lines to occur (36).…”

Vomocytosis: What we know so far

“…Events of lateral transfer have been observed for Scedosporium apiospermum and Lomentospora prolificans (Trzaska, 2018), although due to spore germination, the accepting macrophage is lysed shortly after the event. It is therefore uncertain whether these are bona fide vomocytosis events followed by phagocytosis, as reported for Cryptococcus (Dragotakes et al, 2019), or a different but related process.…”

“…Recently, Dragotakes et al showed that lateral transfer is the combination of a nonlytic exocytosis event followed by phagocytosis by a nearby macrophage (Dragotakes, Fu, & Casadevall, 2019). It is therefore uncertain whether these are bona fide vomocytosis events followed by phagocytosis, as reported for Cryptococcus (Dragotakes et al, 2019), or a different but related process. It is therefore uncertain whether these are bona fide vomocytosis events followed by phagocytosis, as reported for Cryptococcus (Dragotakes et al, 2019), or a different but related process.…”

“…As with vomocytosis, both the transferred cell and macrophage remain undamaged after this event. Recently, Dragotakes et al showed that lateral transfer is the combination of a nonlytic exocytosis event followed by phagocytosis by a nearby macrophage (Dragotakes, Fu, & Casadevall, 2019). Events of lateral transfer have been observed for Scedosporium apiospermum and Lomentospora prolificans (Trzaska, 2018), although due to spore germination, the accepting macrophage is lysed shortly after the event.…”