Expulsion of Live Pathogenic Yeast by Macrophages

Abstract

Phagocytic cells, such as neutrophils and macrophages, perform a critical role in protecting organisms from infection by engulfing and destroying invading microbes . Although some bacteria and fungi have evolved strategies to survive within a phagocyte after uptake, most of these pathogens must eventually kill the host cell if they are to escape and infect other tissues . However, we now demonstrate that the human fungal pathogen Cryptococcus neoformans is able to escape from within macrophages without killing the host cell by a novel expulsive mechanism. This process occurs in both murine J774 cells and primary human macrophages. It is extremely rapid and yet can occur many hours after phagocytosis of the pathogen. Expulsion occurs independently of the initial route of phagocytic uptake and does not require phagosome maturation . After the expulsive event, both the host macrophage and the expelled C. neoformans appear morphologically normal and continue to proliferate, suggesting that this process may represent an important mechanism by which pathogens are able to escape from phagocytic cells without triggering host cell death and thus inflammation .

The small GTPase RAB-11 directs polarized exocytosis of the intracellular pathogen N. parisii for fecal-oral transmission from C. elegans

“…An exocytosis-type process termed "vomocytosis" has been implicated in the exit of fungal pathogens from macrophages (33,34), although this process is likely distinct from the polarized exocytosis used to escape from epithelial cells. Whereas exocytosis has been shown to contribute to bacterial pathogen exit in mammalian tissue culture systems of epithelial cells (35), multiple modes of exit have been proposed for the same pathogen, and the in vivo significance and contribution of exocytosis to disease transmission has not been clear.…”

The Facultative Intracellular Pathogen Candida glabrata Subverts Macrophage Cytokine Production and Phagolysosome Maturation

“…neoformans, by which fungal cells and macrophages remain alive even after the release of yeast cells (25,26): MDMs clearly burst when releasing C. glabrata cells. The process is therefore more comparable to cytolysis, an escape mechanism used by bacterial species such as Chlamydia or Leishmania spp.…”

“…Cr. neoformans can also escape macrophages via extrusion/expulsion (25,26). The formation of massive vacuoles by the fungus is followed by extrusion of the phagosomes and the release of the pathogen.…”

The fatal fungal outbreak on Vancouver Island is characterized by enhanced intracellular parasitism driven by mitochondrial regulation

“…For this assay, J774 macrophage cells or human primary blood-derived macrophage cells [HPBMCs, which were isolated and activated as previously described (36)] were exposed to cryptococci opsonised with 18B7 antibody for 2 h as described in (36). Each well was washed with PBS 4 -5 times to remove as many extracellular yeast cells as possible and 1 mL fresh serum-free DMEM was added.…”