Fungal Infections in Disorders of Inborn Errors of Immunity.

Emerging infectious threats continually challenge the adaptability of the human immune system. Inborn errors of immunity (IEIs) provide a unique framework to dissect host-pathogen interactions, revealing how single-gene defects uncover critical pathways in antifungal defence. This review offers an overview of fungal immunity through the lens of IEIs, and integrates recent advances in innate fungal recognition, neutrophil and mononuclear phagocyte effector mechanisms, CARD9/NF-kB signalling, IL-17/IL-23 and IL-12/IFN-gamma cytokine axes, and transcription-factor defects that shape susceptibility to Candida, Aspergillus, Pneumocystis, Cryptococcus, dimorphic fungi and other moulds. We also discuss acquired phenocopies mediated by anti-cytokine autoantibodies, translate these mechanisms into clinical red flags and diagnostic algorithms, and discuss potential therapeutic strategies. Finally, we highlight how genetically defined IEIs can be used to study fungal-bacterial, fungal-mycobacterial and fungal-viral co-infections, revealing the hierarchy and plasticity of host defence in health and disease.