Immunity to fungal infections

Key Points Fungi can interact with humans in multiple ways, establishing symbiotic, commensal, latent or pathogenic relationships. Although the burdens of fungal diseases may rival those of many of the best-known bacterial diseases, humans have evolved with ubiquitous or commensal fungi in host–fungus relationships that for the most part are positive or neutral. The co-evolution of humans and fungi suggests that complex mechanisms exist to allow the host immune system to respond to fungi and, likewise, that fungi have developed sophisticated mechanisms to antagonize immune responses. Indeed, fungal diseases represent an important paradigm in immunology, as they can result either from lack of recognition or from overactivation of the inflammatory response. We are entering an exciting period of transition from studying the molecular and cellular bases of the virulence of fungal pathogens to determining the mechanisms of immune adaptations that maintain homeostasis with fungi. As the immune system cannot ignore fungi, a fine balance between pro- and anti-inflammatory signals is required for a stable host–fungus relationship, the disruption of which leads to pathological consequences. Thus, the challenge for future studies is to gain a better understanding of the control of inflammation, the molecular bases of regulation and rupture, and the way in which innocuous but opportunistic fungal pathogens maintain 'friendly' relationships, or evade or subvert host inflammation. The use of multidisciplinary approaches, including functional genomics, proteomics and bioinformatics, will have important biomedical implications. These may include the identification of new susceptibility genes, the identification of more accurate biomarkers that predict inflammatory fungal disorders, and the development of multi-pronged therapeutic approaches that target specific inflammatory or metabolic end points in fungal infections and diseases. In this article, Luigina Romani describes the immune mechanisms that have evolved to recognize and respond to fungi. She explains how the failure of either pro-inflammatory or tolerogenic immune responses can lead to the development of fungal diseases. Fungal diseases represent an important paradigm in immunology, as they can result from either a lack of recognition by the immune system or overactivation of the inflammatory response. Research in this field is entering an exciting period of transition from studying the molecular and cellular bas