KU Leuven, Department of Imaging and Pathology, Biomedical MRI / MoSAIC, Leuven, Belgium.
Methods Mol Biol. 2023;2667:197-210. doi: 10.1007/978-1-0716-3199-7_15.
Aspergillus fumigatus and Cryptococcus neoformans species infections are two of the most common life-threatening fungal infections in the immunocompromised population. Acute invasive pulmonary aspergillosis (IPA) and meningeal cryptococcosis are the most severe forms affecting patients with elevated associated mortality rates despite current treatments. As many unanswered questions remain concerning these fungal infections, additional research is greatly needed not only in clinical scenarios but also under controlled preclinical experimental settings to increase our understanding concerning their virulence, host-pathogen interactions, infection development, and treatments. Preclinical animal models are powerful tools to gain more insight into some of these needs. However, assessment of disease severity and fungal burden in mouse models of infection are often limited to less sensitive, single-time, invasive, and variability-prone techniques such as colony-forming unit counting. These issues can be overcome by in vivo bioluminescence imaging (BLI). BLI is a noninvasive tool that provides longitudinal dynamic visual and quantitative information on the fungal burden from the onset of infection and potential dissemination to different organs throughout the development of disease in individual animals. Hereby, we describe an entire experimental pipeline from mouse infection to BLI acquisition and quantification, readily available to researchers to provide a noninvasive, longitudinal readout of fungal burden and dissemination throughout the course of infection development, which can be applied for preclinical studies into pathophysiology and treatment of IPA and cryptococcosis in vivo.
烟曲霉和新生隐球菌属物种感染是免疫功能低下人群中最常见的两种危及生命的真菌感染。急性侵袭性肺曲霉病 (IPA) 和脑膜隐球菌病是最严重的形式,尽管目前有治疗方法,但仍会影响患者的死亡率。由于这些真菌感染仍有许多未解答的问题,不仅在临床情况下,而且在受控的临床前实验环境下,都非常需要额外的研究,以增加我们对其毒力、宿主-病原体相互作用、感染发展和治疗的理解。临床前动物模型是深入了解这些需求的有力工具。然而,感染小鼠模型中疾病严重程度和真菌负担的评估通常仅限于不太敏感、单次、侵入性和易变的技术,如集落形成单位计数。这些问题可以通过体内生物发光成像 (BLI) 来克服。BLI 是一种非侵入性工具,可提供从感染开始到疾病发展过程中不同器官潜在传播的真菌负担的纵向动态视觉和定量信息。在这里,我们描述了从小鼠感染到 BLI 采集和定量的整个实验过程,研究人员可以轻松获得该过程,从而提供对感染发展过程中真菌负担和传播的非侵入性、纵向读数,可应用于 IPA 和隐球菌病的临床前研究。