Curtis Aaron, Binder Ulrike, Kavanagh Kevin
Department of Biology, Maynooth University, Maynooth, Ireland.
Institute of Hygiene and Medical Microbiology, Medical University Innsbruck, Innsbruck, Austria.
Front Fungal Biol. 2022 Apr 26;3:893494. doi: 10.3389/ffunb.2022.893494. eCollection 2022.
larvae have become a widely accepted and utilised infection model due to the functional homology displayed between their immune response to infection and that observed in the mammalian innate immune response. Due to these similarities, comparable results to murine studies can be obtained using larvae in assessing the virulence of fungal pathogens and the toxicity or efficacy of anti-fungal agents. This coupled with their low cost, rapid generation of results, and lack of ethical/legal considerations make this model very attractive for analysis of host-pathogen interactions. The larvae of have successfully been utilised to analyse various fungal virulence factors including toxin and enzyme production providing in depth analysis of the processes involved in the establishment and progression of fungal pathogens (e.g., , and ). A variety of experimental endpoints can be employed including analysis of fungal burdens, alterations in haemocyte density or sub-populations, melanisation, and characterisation of infection progression using proteomic, histological or imaging techniques. Proteomic analysis can provide insights into both sides of the host-pathogen interaction with each respective proteome being analysed independently following infection and extraction of haemolymph from the larvae. can also be employed for assessing the efficacy and toxicity of antifungal strategies at concentrations comparable to those used in mammals allowing for early stage investigation of novel compounds and combinations of established therapeutic agents. These numerous applications validate the model for examination of fungal infection and development of therapeutic approaches in compliance with the need to reduce animal models in biological research.
由于幼虫对感染的免疫反应与哺乳动物先天免疫反应之间存在功能同源性,幼虫已成为一种广泛接受和使用的感染模型。由于这些相似性,在评估真菌病原体的毒力以及抗真菌剂的毒性或疗效时,使用幼虫可以获得与小鼠研究相当的结果。这再加上它们成本低、结果产生迅速,以及不存在伦理/法律问题,使得该模型对于分析宿主-病原体相互作用非常有吸引力。已成功利用幼虫来分析各种真菌毒力因子,包括毒素和酶的产生,从而深入分析真菌病原体建立和进展过程中所涉及的过程(例如,[具体真菌名称1]、[具体真菌名称2]和[具体真菌名称3])。可以采用多种实验终点,包括分析真菌负荷、血细胞密度或亚群的变化、黑化,以及使用蛋白质组学、组织学或成像技术对感染进展进行表征。蛋白质组学分析可以深入了解宿主-病原体相互作用的双方,在感染后从幼虫中提取血淋巴并独立分析各自的蛋白质组。幼虫还可用于评估抗真菌策略在与哺乳动物使用浓度相当的浓度下的疗效和毒性,从而允许对新型化合物和已确立治疗剂的组合进行早期研究。这些众多的应用验证了该模型在检查真菌感染和开发治疗方法方面的有效性,符合减少生物学研究中动物模型的需求。