The fight of innate immunity and abnormal cannabinoids against Candida infection

Candida species represent the most clinically significant fungal pathogens in humans, with invasive candidiasis carrying a mortality of 30%-40% in critically ill patients despite modern antifungal therapy. The innate immune system - through the coordinated and specific activities of neutrophils, macrophages, NK cells, mast cells and eosinophils - constitute the primary and most consequential biological defence against Candida invasion. Abnormal cannabinoids (Abn-CBDs), a structurally distinctive class of synthetic lipid compounds with non-psychoactive properties and regioisomeric configurations, critically distinct from classical cannabinoids in their independence from CB₁ and CB₂ receptor signalling, have emerged as a novel and pharmacologically compelling class of antifungal compounds. This review integrates the current understanding of innate immune cell antifungal mechanisms with the emerging pharmacology of abnormal cannabinoids, examines the direct antifungal and immunomodulatory properties of Abn-CBDs, and critically addresses the tripartite contest between innate immunity, abnormal cannabinoids and Candida's formidable evasion repertoire.