Dangerous Liaisons: Interactions of Cryptococcus neoformans with Host Phagocytes

Abstract

Cryptococcus neoformans is an opportunistic fungal pathogen and a leading cause of death in immunocompromised individuals. The interactions of this yeast with host phagocytes are critical to disease outcome, and C. neoformans is equipped with an array of factors to modulate these processes. Cryptococcal infection begins with the deposition of infectious particles into the lungs, where the fungal cells deploy various antiphagocytic factors to resist internalization by host cells. If the cryptococci are still engulfed, they can survive and proliferate within host cells by modulating the phagolysosome environment in which they reside. Lastly, cryptococcal cells may escape from phagocytes by host cell lysis, nonlytic exocytosis, or lateral cell-to-cell transfer. The interactions between C. neoformans and host phagocytes also influence the dissemination of this pathogen to the brain, where it may cross the blood-brain barrier and cause an often-fatal meningoencephalitis. In this review, we highlight key cryptococcal factors involved in various stages of cryptococcal-host interaction and pathogenesis.

Keywords: Cryptococcus neoformans; Trojan horse transit; host-pathogen interactions; non-lytic exocytosis; pathogenesis; phagocytes.

Figure 1

C. neoformans interactions with host cells. Left, inhalation of infectious particles and dissemination to the brain. Right, events discussed in the text: Top, blood-brain barrier (BBB) traversal by C. neoformans may be paracellular (i), transcellular (ii), or via Trojan horse transit (iii). Bottom, possible fates of C. neoformans after engulfment include fungal clearance (a), proliferation (b), lytic escape (c), nonlytic exocytosis (d), and cell-to-cell transfer (e).

Figure 2

Schematic of cryptococcal features discussed in the text that influence interactions with host cells. See text for details. Concentric cellular regions: brown, nucleus; pale orange, cytosol; bright orange, cell wall; beige, capsule. Labeled ovals: light blue, transcription factors; dark blue, intracellular proteins; purple, plasma membrane/cell wall proteins; maroon, secreted proteins. CnMVs, cryptococcal microvesicles.