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评价一种用于研究皮肤癣菌红色毛癣菌感染的猪皮模型。

Evaluation of an Explanted Porcine Skin Model to Investigate Infection with the Dermatophyte Trichophyton rubrum.

机构信息

Department of Pharmacy and Pharmacology, University of Bath, Bath, BA2 7AY, UK.

出版信息

Mycopathologia. 2020 Apr;185(2):233-243. doi: 10.1007/s11046-020-00438-9. Epub 2020 Feb 27.

Abstract

Dermatophytosis is a fungal infection of skin, hair and nails, and the most frequently found causative agent is Trichophyton rubrum. The disease is very common and often recurring, and it is therefore difficult to eradicate. To develop and test novel treatments, infection models that are representative of the infection process are desirable. Several infection models have been developed, including the use of cultured cells, isolated corneocytes, explanted human skin or reconstituted human epidermis. However, these have various disadvantages, ranging from not being an accurate reflection of the site of infection, as is the case with, for example, cultured cells, to being difficult to scale up or having ethical issues (e.g., explanted human skin). We therefore sought to develop an infection model using explanted porcine skin, which is low cost and ethically neutral. We show that in our model, fungal growth is dependent on the presence of skin, and adherence of conidia is time-dependent with maximum adherence observed after ~ 2 h. Scanning electron microscopy suggested the production of fibril-like material that links conidia to each other and to skin. Prolonged incubation of infected skin leads to luxurious growth and invasion of the dermis, which is not surprising as the skin is not maintained in conditions to keep the tissue alive, and therefore is likely to lack an active immune system that would limit fungal growth. Therefore, the model developed seems useful to study the early stages of infection. Furthermore, we demonstrate that the model can be used to test novel treatment regimens for tinea infections.

摘要

皮肤癣菌病是一种皮肤、毛发和指甲的真菌感染,最常发现的病原体是红色毛癣菌。这种疾病非常常见且经常复发,因此很难根除。为了开发和测试新的治疗方法,需要开发能够代表感染过程的新型感染模型。已经开发了几种感染模型,包括使用培养细胞、分离的角质细胞、离体人皮肤或重建的人表皮。然而,这些模型存在各种缺点,从不能准确反映感染部位(例如培养细胞)到难以规模化或存在伦理问题(例如离体人皮肤)。因此,我们试图开发一种使用离体猪皮的感染模型,这种模型成本低且在伦理上是中立的。我们表明,在我们的模型中,真菌的生长依赖于皮肤的存在,并且附着于孢子是时间依赖性的,最大附着发生在大约 2 小时后。扫描电子显微镜表明产生了纤维状物质,将孢子相互连接并与皮肤连接。感染皮肤的长时间孵育会导致奢侈生长和真皮的入侵,这并不奇怪,因为皮肤没有处于维持组织存活的条件下,因此可能缺乏能够限制真菌生长的主动免疫系统。因此,开发的模型似乎可用于研究感染的早期阶段。此外,我们证明该模型可用于测试癣感染的新型治疗方案。

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