Assessment of the cutaneous immune response during Arthroderma benhamiae and A. vanbreuseghemii infection using an experimental mouse model.

BACKGROUND: Dermatophytoses are common but poorly understood skin infections. Most in vivo studies have been performed using the guinea pig as the experimental animal model, which has several limitations. OBJECTIVES: To develop a mouse model of dermatophytosis suitable for multiple purposes, including the investigation of immunity against dermatophytes. MATERIALS AND METHODS: Two peculiar fungal species, Arthroderma benhamiae and A. vanbreuseghemii, isolated from tinea in humans having contact with rodents were used for epicutaneous inoculation. During the infection, clinical and histopathological follow-up were performed. The recruitment of immune cells was evaluated by immunofluorescence staining and the levels of cytokine mRNA were quantified by quantitative reverse transcriptase-polymerase chain reaction in the skin of infected mice. RESULTS: The skin symptoms and microscopic lesions, including the colonization of keratinized epidermal and follicular structures by both dermatophytes, were highly similar to those observed in guinea pig infection models and in natural infections, mimicking acute superficial tinea in humans. The dermal inflammatory cellular infiltrate consisted of macrophages, dendritic cells and especially polymorphonuclear neutrophils, which are one of the histological 'clues' to the diagnosis of dermatophytosis. The in situ cytokine profile was characterized by the overexpression of transforming growth factor-ß, interleukin (IL)-1ß and IL-6 mRNA during infection, suggesting a role of the T-helper 17 pathway in the establishment of immunity. CONCLUSIONS: Our new reproducible and validated mouse model of dermatophytosis is a modern in vivo tool that allows a more in-depth understanding of the pathogenesis of human dermatophyte infections.

Mechanisms of skin adherence and invasion by dermatophytes.

Dermatophytes 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.