Despite the superficial localization of most dermatophytosis, host-fungus relationship in these infections is complex and still poorly elucidated. Though many efforts have been accomplished to characterize secreted dermatophytic proteases at the molecular level, only punctual insights have been afforded into other aspects of the pathogenesis of dermatophytosis, such as fungal adhesion, regulation of gene expression during the infection process, and immunomodulation by fungal factors. However, new genetic tools were recently developed, allowing a more rapid and high-throughput functional investigation of dermatophyte genes and the identification of new putative virulence factors. In addition, sophisticated in vitro infection models are now used and will open the way to a more comprehensive view of the interactions between these fungi and host epidermal cells, especially keratinocytes.
SummaryDermatophytes are keratinophilic fungi that can be pathogenic for humans and animals by infecting the stratum corneum, nails, claws or hair. The first infection step consists of adherence of arthroconidia to the stratum corneum. The mechanisms and the kinetics of adherence have been investigated using different in vitro and ex vivo experimental models, most notably showing the role of a secreted serine protease from Microsporum canis in fungal adherence to feline corneocytes. After germination of the arthroconidia, dermatophytes invade keratinised structures that have to be digested into short peptides and amino acids to be assimilated. Although many proteases, including keratinolytic ones, have been characterised, the understanding of dermatophyte invasion mechanisms remains speculative. To date, research on mechanisms of dermatophyte infection focused mainly on both secreted endoproteases and exoproteases, but their precise role in both fungal adherence and skin invasion should be further explored.
RNA interference is a useful tool to evaluate pathogenic mechanisms of M. canis. For the first time, a role in pathogenicity could be attributed to a protease of a dermatophyte, namely Sub3 from M. canis, which is required for adherence to but not for invasion of the epidermis.
The growth of knowledge concerning all aspects of the host-dermatophyte relationship should contribute towards sound strategies for the development of effective and safe vaccines against dermatophytosis.
Microsporum canis is a pathogenic fungus that causes a superficial cutaneous infection called dermatophytosis, mainly in cats and humans. The mechanisms involved in adherence of M. canis to epidermis have never been investigated. Here, a model was developed to study the adherence of M. canis to feline corneocytes through the use of a reconstructed interfollicular feline epidermis (RFE). In this model, adherence of arthroconidia to RFE was found to be time-dependent, starting at 2 h post-inoculation and still increasing at 6 h. Chymostatin, a serine protease inhibitor, inhibited M. canis adherence to RFE by 53 %. Moreover, two mAbs against the keratinolytic protease subtilisin 3 (Sub3) inhibited M. canis adherence to RFE by 23 %, suggesting that subtilisins, and Sub3 in particular, are involved in the adherence process.
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