TH17 Cells in Fungal Infections

Although TH1 responses driven by the IL-12/IFN-gamma axis are central to protection against fungi, the paradigm has been revisited with two new T cell populations entering the scene: the TH17 cells involved in inflammatory responses, and the T regulatory cells (Tregs), which minimize immune responses to avoid damage to the host. While many studies have focused on the pathological aspects of IL-17-producing T cells in many auto-immune diseases, their role in protective anti-microbial immunity has also been increasingly recognized. Some degree of inflammation is required for protection, particularly in mucosal tissues during the transitional response occurring between the rapid innate and slower adaptive response. However, progressive inflammation worsens disease, limits protective antifungal immune responses and ultimately prevents pathogen eradication. In this scenario, deregulated activity of TH17 cells and Tregs in mediating and restraining inflammation may occur. The enzyme indoleamine 2, 3-dioxygenase and tryptophan metabolites crucially contribute to immune homeostasis by limiting TH17 cell activation and inducing Tregs-taming heightened inflammatory responses. The new findings support a view in which the immune system tailors protective responses to suit infecting fungi while limiting host damage through distinct modules of immunity.