Macrophages use sub-micron actin ridges in phagocytosis of encapsulated fungal pathogens

Abstract

Ingestion and killing of pathogens by phagocytic cells is a key aspect of animal immunity. Cryptococcus neoformans is a major pathogen of AIDS patients that has a polysaccharide capsule that is critical for virulence. Phagocytic function is necessary for normal immunity to cryptococcal infection, and we sought to determine how Cryptococcus capsule prevents phagocytosis. In doing so, we discovered a new sub-micron actin structure, the ridge, that is present on macrophages, neutrophils and amoebae. Macrophages preferentially bind cryptococci via ridges and suppression of ridges is sufficient to prevent phagocytosis. Ridges are present on macrophages in vivo and are lost in interleukin 10 stimulated macrophages. The discovery and functional description of macrophage surface ridges fills a critical gap in our understanding of how phagocytes ingest encapsulated fungal pathogens, a crucial step in treating infection.