Phagosome maturation during fungal infection

The phagosome is a dynamic organelle whose function is defined by engulfment and elimination of particles, including debris, dead cells, and foreign material such as invading pathogens. To effectively contain, kill, and degrade pathogens, the phagosome undergoes highly coordinated maturation through interaction with proteins, second messengers, and other organelles in the endocytic pathway. This process involves a progressive decrease in luminal pH as the phagosome fuses with other endocytic vesicles and lysosomes. While diverse pathogens may trigger different mechanisms of phagosome maturation or interfere with these processes, this review focuses on host processes that lead to the successful maturation of macrophage phagosomes containing fungal pathogens (hereafter referred to as fungal phagosomes). Fungal pathogens are unique in that they are comparatively very large infectious particles and can undergo rapid growth within the phagosome. However, phagosome maturation maintains phagosomal membrane integrity, allowing phagocytes to hinder fungal growth and exert microbicidal activity within this hostile compartment. Recent findings suggest that phagosome maturation depends on interaction with other organelles, such as the endoplasmic reticulum. Additionally, roles for mitochondria are also emerging for the regulation of fungicidal activity within the phagosome. As these processes are crucial for successful host defense during fungal pathogen infection, modulation fungal phagosome maturation and function is a promising direction for host-directed therapeutics to treat fungal infection.