Mechanisms of immune evasion in fungal pathogens

The incidence of life-threatening fungal infections has continued to increase in recent years, predominantly in patients debilitated by iatrogenic interventions or immunological dysfunctions. While the picture of the immunology of fungal infections grows increasingly complex, it is clear that the phagocyte–pathogen interaction is a critical determinant of establishing an infection. About 10 years ago, genome-scale approaches began to elucidate the intricate and extensive fungal response to phagocytosis and in the last few years it has become clear that some of this response actively modulates immune cell function. Fungal pathogens avoid detection by masking pathogen-associated molecular patterns, such as cell wall carbohydrates, and by downregulating the complement cascade. Once detected, various species interfere with phagocytosis and intracellular trafficking, and can repress production of antimicrobials like nitric oxide (NO). For the most part, the molecular mechanisms behind these behaviors are not yet known. This review discusses recent discoveries and insights into how fungi manipulate the host–pathogen interaction.

► Fungal pathogens use a variety of mechanisms to subvert the immune response. ► Many species bind mammalian regulatory factors that inhibit the complement cascade. ► Many fungal pathogens block NO production from phagocytes through unknown mechanisms. ► Fungi can interdict normal phagolysosome maturation in multiple ways.