Interactions of fungal pathogens with phagocytes

Key Points Several mechanisms exist by which fungi can delay or interfere with the processes used by phagocytic cells of the innate immune system to uptake and kill invading cells. Certain fungal species escape immune capture by generating cell types, such as Titan cells, elongated tubular hyphae or sporulating structures, known as spherules, that are too large to be taken up by phagocytic cells and cannot be killed by phagocytosis. Fungal cell wall layers are highly heterogeneous and include components such as hydrophobic proteins and α-glucan that do not activate immune receptors and hence cloak other wall components that would otherwise result in detection by the host immune system. Fungal pathogens can rapidly alter the composition of their cell walls when growing in the host where they are exposed to different nutrients and environmental conditions, or when undergoing morphogenesis. This makes them a moving target for immune detection. Many fungi are able to induce their own exocytosis after they have been taken up by macrophages. The formation of hyphae by Candida albicans is induced within phagosomes and this activates a modified form of programmed cell death known as pyroptosis. This process, and the physical rupture of the phagocyte membrane by growing hyphae, can eliminate a proportion of innate immune cells that would otherwise confer protection to the host. Some fungi interfere with the mechanism of phagosome maturation, preventing or delaying the fusion of vesicles which contain microbicidal compounds that are required for fungal killing. Phagocytes can detect and eliminate fungal pathogens, but fungi have evolved several mechanisms that enable them to subvert immune recognition, uptake and killing. In this Review, Erwig and Gow detail how fungi interact with the host innate immune system and describe the mechanisms of immune evasion used by fungal pathogens to promote infection. The surveillance and elimination of fungal pathogens rely heavily on the sentinel behaviour of phagocytic cells of the innate immune system, especially macrophages and neutrophils. The efficiency by which these cells recognize, uptake and kill fungal pathogens depends on the size, shape and composition of the fungal cells and the success or failure of various fungal mechanisms of immune evasion. In this Review, we describe how fungi, particularly Candida albicans , interact with phagocytic cells and discuss the many factors that contribute to fungal immune evasion and