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Immunomodulatory functions of fungal melanins in respiratory infections

Summary

Some dangerous fungi produce a dark pigment called melanin that acts like a cloak, protecting them from the body’s immune system. This review explains how melanin blocks multiple immune defenses, including suppressing warning signals to immune cells, preventing immune cells from engulfing and killing the fungi, and even absorbing harmful reactive molecules. Understanding these sneaky tactics could help scientists develop new treatments that strip away this protective cloak, making the fungi vulnerable to both the body’s natural defenses and antifungal drugs.

Background

Invasive fungal infections have increased significantly with high mortality rates, and current antifungal therapies are limited. Fungal melanins are cell wall components that serve as virulence factors in pathogenic fungi. Understanding how melanin dysregulates innate immune function is critical for developing new therapeutic strategies.

Objective

To comprehensively review the role of fungal melanin as a virulence factor through its immunomodulatory effects during respiratory infections. The review examines how melanized fungi including Aspergillus, Cryptococcus, and Rhizopus subvert host immune responses through melanin-mediated mechanisms.

Results

Fungal melanin blocks epithelial chemokine secretion, inhibits LC3-associated phagocytosis (LAP), reprograms macrophage metabolism toward glycolysis, sequesters calcium, binds complement components, interferes with surfactant function, and absorbs reactive oxygen species. Both DHN-melanin and L-DOPA melanin employ similar immunosuppressive mechanisms despite their different biosynthetic origins.

Conclusion

Fungal melanins function as potent virulence factors that directly modulate multiple host immune functions through both direct binding and indirect pathways. Targeting fungal melanin synthesis or developing anti-melanin therapies represents a promising strategy for enhancing antifungal immunity and potentially improving clinical outcomes in fungal infections.
  • Published in:mBio,
  • Study Type:Review,
  • Source: 10.1128/mbio.02141-25, PMID: 41378875
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