Challenges posed by fungi to host immunity: Mechanisms of immune evasion

Immune evasion involves strategies that pathogens use to escape detection and removal by the host immune system, particularly pronounced in fungal infections. As ancient eukaryotic organisms, fungi have developed distinct structural characteristics, immunoregulatory molecules, and intricate immune evasion strategies that enable survival and proliferation in complex immune environments. This review summarizes the primary mechanisms of fungal immune evasion and the resulting challenges to the host immune system, including the antigenic variation of surface polysaccharides, suppression of host immune cell functions, and the formation of biofilms that resist immune clearance. Furthermore, fungi can exploit negative regulatory signaling pathways within host immune cells to enhance their survival and reproduction. Importantly, genetic deficiencies in the host have been linked to increased susceptibility to fungal infections. This review also explores emerging therapeutic avenues, including the repurposing of existing drugs and novel immunotherapeutic strategies aimed at counteracting specific evasion mechanisms. A comprehensive understanding of these processes is essential for developing more effective antifungal therapies and improving infection outcomes. • Fungal immune evasion driven by structural adaptations like β-glucan masking. • Active immunosuppression via interleukin-1 receptor antagonist (IL-1Ra) and complement interference. • Host susceptibility induced by negative regulatory pathway dysregulation and genetic polymorphisms. • Drug repurposing to target immune evasion offers promising therapeutic avenue against infections.