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

被引:32
作者
Cambier, L. [1 ]
Weatherspoon, A. [3 ]
Defaweux, V. [3 ]
Bagut, E. T. [1 ,4 ]
Heinen, M. P. [1 ]
Antoine, N. [2 ]
Mignon, B. [1 ]
机构
[1] Univ Liege, Vet Mycol Lab, Dept Infect & Parasit Dis, B-4000 Liege, Belgium
[2] Univ Liege, Vet Histol Lab, Dept Morphol & Pathol, Fac Vet Med, B-4000 Liege, Belgium
[3] CHU Liege, Human Histol Lab, Dept Preclin Sci, Fac Med, Liege, Belgium
[4] Univ Agr Sci & Vet Med Cluj Napoca, Parasitol & Parasit Dis Unit, Fac Vet Med, Cluj Napoca, Romania
关键词
EXPERIMENTAL MURINE DERMATOPHYTOSIS; CELL-MEDIATED-IMMUNITY; TRICHOPHYTON-QUINCKEANUM; MICROSPORUM-CANIS; NEUTROPHIL RECRUITMENT; HOST-DEFENSE; IL-17; INFLAMMATION; ACTIVATION; INNATE;
D O I
10.1111/bjd.12673
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
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-β, interleukin (IL)-1β 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. What's already known about this topic? Pathophysiology and immunology of dermatophytoses are still poorly understood. Most in vivo studies have been performed using guinea pig-based models. Several limitations, notably the lack of immunological tools for this animal species, render the development of a modern mouse model necessary for progress in the understanding of pathogenesis. What does this study add? Using two peculiar fungal species isolated from humans, Arthroderma benhamiae and A. vanbreuseghemii, a new mouse model of dermatophytosis was developed. Clinical, histopathological and immunohistological evaluations showed that this model is reproducible, fits with previous experimental infection models using guinea pigs and mimics superficial tinea in humans. For the first time, the cutaneous cytokine response was assessed during a dermatophyte infection, showing that the role of the T-helper 17 pathway should now be considered. © 2013 British Association of Dermatologists.
引用
收藏
页码:625 / 633
页数:9
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