Emerging Bacterial Pathogens Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy.
Centre of Statistics for Biomedical Sciences (CUSSB), Vita-Salute San Raffaele University, 20132 Milan, Italy.
Int J Mol Sci. 2020 Sep 9;21(18):6590. doi: 10.3390/ijms21186590.
Pulmonary infections caused by (MA) have increased over recent decades, affecting individuals with underlying pathologies such as chronic obstructive pulmonary disease, bronchiectasis and, especially, cystic fibrosis. The lack of a representative and standardized model of chronic infection in mice has limited steps forward in the field of pulmonary infection. To overcome this challenge, we refined the method of agar beads to establish chronic infection in immunocompetent mice. We evaluated bacterial count, lung pathology and markers of inflammation and we performed longitudinal studies with magnetic resonance imaging (MRI) up to three months after infection. In this model, was able to establish a persistent lung infection for up to two months and with minimal systemic spread. Lung histopathological analysis revealed granulomatous inflammation around bronchi characterized by the presence of lymphocytes, aggregates of vacuolated histiocytes and a few neutrophils, mimicking the damage observed in humans. Furthermore, lung lesions were successfully monitored for the first time by MRI. The availability of this murine model and the introduction of the successfully longitudinal monitoring of the murine lung lesions with MRI pave the way for further investigations on the impact of pathogenesis and the efficacy of novel treatments.
近年来,由 (MA)引起的肺部感染有所增加,影响了患有慢性阻塞性肺疾病、支气管扩张症等基础病理的个体,尤其是囊性纤维化。缺乏具有代表性和标准化的慢性感染小鼠模型,限制了肺部感染领域的进展。为了克服这一挑战,我们改进了琼脂珠方法,在免疫功能正常的小鼠中建立了慢性感染。我们评估了细菌计数、肺部病理学和炎症标志物,并进行了长达三个月的磁共振成像 (MRI) 纵向研究。在该模型中, 能够建立长达两个月的持续性肺部感染,且全身扩散最小。肺部组织病理学分析显示,支气管周围存在肉芽肿性炎症,特征是淋巴细胞、空泡化组织细胞聚集和少量中性粒细胞,类似于人类观察到的损伤。此外, 肺部病变首次通过 MRI 成功监测到。该小鼠模型的出现以及成功地对小鼠肺部病变进行长期 MRI 监测,为进一步研究 发病机制和新型治疗方法的疗效铺平了道路。