IL-17-Mediated Immunity to the Opportunistic Fungal Pathogen Candida albicans

Abstract

IL-17 (IL-17A) has emerged as a key mediator of protection against extracellular microbes, but this cytokine also drives pathology in various autoimmune diseases. Overwhelming data in both humans and mice reveal a clear and surprisingly specific role for IL-17 in protection against the fungus Candida albicans, a commensal microbe of the human oral cavity, gastrointestinal tract, and reproductive mucosa. The IL-17 pathway regulates antifungal immunity through upregulation of proinflammatory cytokines, including IL-6, neutrophil-recruiting chemokines (e.g., CXCL1 and CXCL5), and antimicrobial peptides (e.g., defensins), which act in concert to limit fungal overgrowth. This review focuses on diseases caused by C. albicans, the role of IL-17-mediated immunity in candidiasis, and the implications for clinical therapies for both autoimmune conditions and fungal infections.

Figure 1. Adaptive and Innate Immune Responses to C. albicans

C. albicans exists in various morphologies, which are sensed by PRRs such as C-type lectin receptors found on APCs as well as epithelial cells. Exposure to C. albicans induces expression of innate cytokines, many of which are inductive for IL-17-expression cells. Various sources of IL-17 are documented in the context of candidiasis, including innate and adaptive cell types. IL-17 signaling on epithelial or other non-hematopoietic cells leads to expression of chemokines, AMPs and other factors that contribute to fungal control.