Vitamin D's role in antifungal immunity remains uncertain due to species differences

Vitamin D–mediated regulation of antimicrobial peptides (AMPs) is an important focus in innate immunology and is aimed at elucidating the role of vitamin D in enhancing antimicrobial defense. AMPs are short protein chains that serve as a first line of defense against invading pathogens, including fungi, bacteria and viruses. Unlike conventional antibiotics, AMPs are produced endogenously and are less likely to induce antimicrobial resistance, making them promising candidates for treating infections caused by drug-resistant pathogens. Studies indicate that optimal vitamin D levels are essential for activating antimicrobial pathways and regulating AMPs that target multiple fungal pathogens. This article summarizes recent findings on vitamin D-induced AMPs in the context of invasive fungal infections. It also distinguishes vitamin D as a host immune modulator from vitamin D3 as a putative active antifungal compound, given that direct antifungal use is limited by supraphysiologic dosing requirements, pharmacologic impracticality, and risks of hypercalcemia and hyperphosphatemia, especially in patients with granulomatous diseases. Model limitations and species differences are also discussed, including primate-specific CAMP vitamin D response element regulation, which constrains direct translation of rodent vitamin D-to-LL-37 findings to human fungal disease. Current global fungal priority frameworks and resistance surveillance support emphasizing Candida, Aspergillus, and Cryptococcus in this review of invasive fungal disease and translational host-defense evidence, underscoring the relevance of these pathogens.