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Divergent Immunomodulatory Roles of Fungal DNA in Shaping Treg and Inflammatory Responses

Summary

Different types of fungal DNA trigger different immune responses in the body. DNA from the common yeast Candida albicans promotes immune tolerance and protects T cells, similar to beneficial bacterial DNA. In contrast, DNA from the pathogenic fungus Cryptococcus neoformans triggers strong inflammatory immune responses. This discovery reveals that fungal DNA itself, not just fungal cell wall components, plays an important role in determining whether fungi are treated as friendly commensals or dangerous pathogens by the immune system.

Background

Fungal communities in the gut influence host immunity, yet most research has focused on cell wall components rather than fungal genetic material. This study explores how fungal genomic DNA from different fungal species modulates immune responses in human and murine immune cells.

Objective

To investigate how genomic DNA from commensal and pathogenic fungi (Candida albicans, Saccharomyces cerevisiae, and Cryptococcus neoformans) differentially modulate regulatory T cell development and inflammatory responses in human CD4+ T cells, murine splenocytes, and macrophages.

Results

C. albicans gDNA promoted Treg development and IL-10 production, preserving CD4+ T cell viability in inflammatory settings. S. cerevisiae gDNA induced moderate Treg responses with restrained effector T cell expansion and higher checkpoint gene expression. C. neoformans gDNA elicited strongly inflammatory responses promoting Th1/Th17 cells with robust activation of DNA-sensing pathways.

Conclusion

Fungal genomic DNA acts as a species-specific immunomodulatory signal that influences whether the immune system adopts tolerant or inflammatory responses toward fungi. These findings highlight fungal DNA as a regulator of host-fungus interactions relevant to commensal persistence, pathogenic invasion, and potential DNA-based antifungal interventions.
  • Published in:Journal of Fungi (Basel),
  • Study Type:Experimental Research,
  • Source: PMC12653120, PMID: 41295141
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