New insights into host-dermatophyte interactions: pathogenesis, host defense mechanisms, and emerging clinical...

Superficial dermatophyte infections are a common cause of fungal diseases worldwide. These filamentous fungi specialize in degrading keratinized tissues (skin, hair, nails) and show an evolutionary trajectory from zoophilic species to anthropophilic species. In recent years, major human pathogens have emerged from the Trichophyton genus, such as T. indotineae, causing outbreaks of chronic, extensive, and difficult-to-treat dermatophytoses. Herein, we discuss recent findings on host-dermatophyte interactions with a focus on Trichophyton. Since the establishment of infection models that have helped to uncover virulence factors in adhesion, germination, and tissue invasion, new research highlights the role of the transcriptional factor StuA and the serine protease subtilisin 6 in dermatophyte pathogenesis. We also emphasize dermatophyte immunity, as clinicians increasingly encounter patients with chronic infections or, in rare instances, patients with deep and disseminated infections. Although keratinocytes mediate early host defense mechanisms, it is apparent that T-cells, specifically T-helper (Th) cells 1 and 17, are required for controlling dermatophytosis. This protective response is characterized by IFN-γ and IL-17, as well as a delayed-type skin hypersensitivity reaction. By contrast, a skewed Th2-type response - marked by IL-4, IgE, and dermatophyte-specific IgG - is often associated with a worsened clinical prognosis, including the development of chronicity and exacerbation of atopic conditions. Through genomic sequencing, CARD9 was identified as a key signaling molecule in dermatophyte immunity and is linked to the development of deep dermatophytosis, possibly leading to extracutaneous disseminations. Further research efforts are warranted to decipher these complex interactions and to develop new treatment strategies.