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.
Highlights
Cryptococcus neoformans is an important fungal pathogen that primarily infects immunocompromised individuals, those with HIV
Free yeast cells or infected phagocytes may subsequently disseminate to other body compartments, traverse the blood-brain barrier, and enter the central nervous system, which can lead to life-threatening fungal meningitis (Figure 1)
Phagocyte lysis has been observed in cryptococcal infections [66,67], even though C. neoformans does not express the pore-forming proteins used by other pathogens for this process [68]
Summary
Cryptococcus neoformans is an important fungal pathogen that primarily infects immunocompromised individuals, those with HIV. Cryptococcal infection begins with the inhalation of spores or desiccated yeasts and their deposition into the alveoli, where they may be internalized by host phagocytes. Cryptococci survive and proliferate within host phagocytic cells and may later escape via various strategies. Free yeast cells or infected phagocytes may subsequently disseminate to other body compartments, traverse the blood-brain barrier, and enter the central nervous system, which can lead to life-threatening fungal meningitis (Figure 1). Most animal models of cryptococcosis have used yeast inoculation withinoculation spores from some strains thatsome appear to be that avirulent as to yeasts can causeasfatal disease cells. The spores or of yeasts are the dominant particle in natural infection open. Question whether spores or yeasts are the dominant particleremains in natural infection remains open
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