Center for Emerging Pathogens, Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ 07103, USA.
Department of Pharmaceutical Sciences, University of New Mexico, Albuquerque, NM 87131, USA.
Dis Model Mech. 2021 Oct 1;14(10). doi: 10.1242/dmm.049018. Epub 2021 Oct 26.
Tuberculosis (TB) treatment regimens are lengthy, causing non-adherence to treatment. Inadequate treatment can lead to relapse and the development of drug resistance TB. Furthermore, patients often exhibit residual lung damage even after cure, increasing the risk for relapse and development of other chronic respiratory illnesses. Host-directed therapeutics are emerging as an attractive means to augment the success of TB treatment. In this study, we used C3HeB/FeJ mice as an experimental model to investigate the potential role of rapamycin, a mammalian target of rapamycin inhibitor, as an adjunctive therapy candidate during the treatment of Mycobacterium tuberculosis infection with moxifloxacin. We report that administration of rapamycin with or without moxifloxacin reduced infection-induced lung inflammation, and the number and size of caseating necrotic granulomas. Results from this study strengthen the potential use of rapamycin and its analogs as adjunct TB therapy, and importantly underscore the utility of the C3HeB/FeJ mouse model as a preclinical tool for evaluating host-directed therapy candidates for the treatment of TB.
结核病（TB）治疗方案漫长，导致治疗不依从。治疗不足可导致复发和耐药性结核病的发展。此外，即使在治愈后，患者通常仍会出现肺部残留损伤，增加复发和其他慢性呼吸道疾病的风险。宿主导向治疗作为增强结核病治疗成功的一种有吸引力的手段正在出现。在这项研究中，我们使用 C3HeB/FeJ 小鼠作为实验模型，研究雷帕霉素（一种哺乳动物雷帕霉素靶蛋白抑制剂）在莫西沙星治疗结核分枝杆菌感染时作为辅助治疗候选药物的潜在作用。我们报告称，雷帕霉素联合或不联合莫西沙星可减轻感染引起的肺部炎症以及干酪样坏死性肉芽肿的数量和大小。这项研究的结果加强了雷帕霉素及其类似物作为辅助结核病治疗的潜力，并强调了 C3HeB/FeJ 小鼠模型作为评估宿主导向治疗候选药物治疗结核病的临床前工具的实用性。
