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Purpose of Review <p>This study aimed to elucidate the cellular and molecular mechanisms underlying the interaction between macrophages and <i>Trichophyton rubrum</i> in the presence of a curcumin analog.</p> Recent Findings <p>RNA-seq and transcriptomic analyses of mRNA and microRNAs using the co-culture model revealed that the presence of <i>T. rubrum</i> strongly modulates gene expression in THP-1 cells, with dozens of genes being upregulated or downregulated (involving signaling pathways, cell communication, inflammation, and immune response). Additionally, the co-culture model can be used to evaluate the response of macrophages infected with <i>T. rubrum</i> in the presence of novel antifungal molecules.</p> Summary <p><i>Trichophyton rubrum</i> is the primary causative agent of superficial mycoses worldwide; however, it has been increasingly associated with invasive infections, particularly in immunocompromised and diabetic patients. Curcumin analogs exhibit promising antifungal and anti-inflammatory activity. The invasive infectious process involves initial contact between the pathogen and the host, pathogen adherence, tissue invasion, and activation of the immune response. Nevertheless, this process remains incompletely understood, especially in the presence of new antifungal compounds. A co-culture model was established using previously germinated and heat-inactivated <i>T. rubrum</i> conidia in contact with THP-1 exposed to curcumin analog for 24 h. This study demonstrated that the synthetic curcuminoid 2102 exhibits potent antifungal activity against <i>T. rubrum,</i> with low minimum inhibitory concentration and reduced cytotoxicity in THP-1-derived macrophages. In co-culture, curcuminoid was able to modulate the inflammatory response, significantly decreasing the release of IL-1β, IL-12, and TNF-α, while promoting a dose-dependent increase in the production of reactive oxygen species, suggesting a dual role in both controlling fungal growth and enhancing cellular defense mechanisms. These findings highlight the potential of the curcuminoid 2102 as a promising candidate for the development of novel antifungal therapies, especially in the context of drug-resistant dermatophyte infections.</p>

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Antifungal, Antioxidant, and Anti-inflammatory Activities of Curcuminoids Toward Macrophages and Trichophyton rubrum Co-culture

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月19日

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  • Vanessa Inácia Borges de Sousa,
  • Arthur de Paula Leão,
  • Marina Fonseca Rahal,
  • Luana Morandi Marambello,
  • Jonathan Dimmock,
  • Mozart Marins,
  • Ana Lúcia Fachin

摘要

Purpose of Review

This study aimed to elucidate the cellular and molecular mechanisms underlying the interaction between macrophages and Trichophyton rubrum in the presence of a curcumin analog.

Recent Findings

RNA-seq and transcriptomic analyses of mRNA and microRNAs using the co-culture model revealed that the presence of T. rubrum strongly modulates gene expression in THP-1 cells, with dozens of genes being upregulated or downregulated (involving signaling pathways, cell communication, inflammation, and immune response). Additionally, the co-culture model can be used to evaluate the response of macrophages infected with T. rubrum in the presence of novel antifungal molecules.

Summary

Trichophyton rubrum is the primary causative agent of superficial mycoses worldwide; however, it has been increasingly associated with invasive infections, particularly in immunocompromised and diabetic patients. Curcumin analogs exhibit promising antifungal and anti-inflammatory activity. The invasive infectious process involves initial contact between the pathogen and the host, pathogen adherence, tissue invasion, and activation of the immune response. Nevertheless, this process remains incompletely understood, especially in the presence of new antifungal compounds. A co-culture model was established using previously germinated and heat-inactivated T. rubrum conidia in contact with THP-1 exposed to curcumin analog for 24 h. This study demonstrated that the synthetic curcuminoid 2102 exhibits potent antifungal activity against T. rubrum, with low minimum inhibitory concentration and reduced cytotoxicity in THP-1-derived macrophages. In co-culture, curcuminoid was able to modulate the inflammatory response, significantly decreasing the release of IL-1β, IL-12, and TNF-α, while promoting a dose-dependent increase in the production of reactive oxygen species, suggesting a dual role in both controlling fungal growth and enhancing cellular defense mechanisms. These findings highlight the potential of the curcuminoid 2102 as a promising candidate for the development of novel antifungal therapies, especially in the context of drug-resistant dermatophyte infections.