Harding Jeffrey S, Schreiber Heidi A, Sandor Matyas
Laboratory Medicine, Department of Pathology, School of Medicine and Public Health, University of Wisconsin Madison, WI, USA.
Front Microbiol. 2011 Dec 12;2:245. doi: 10.3389/fmicb.2011.00245. eCollection 2011.
The host-pathogen biology during infection with Mycobacterium tuberculosis is incredibly complex and despite accelerating progress in research, remains poorly understood. Our limited understanding hinders the development of new drugs, next generation vaccines, and novel therapies. The granuloma is the site where mycobacteria are both controlled and allowed to persist, but it remains one of the least studied aspects of the host-pathogen relationship. Here, we review the development, application, potential uses, and limitations of a novel model of granuloma transplantation as a tool to study specific host-pathogen interactions that have been difficult to probe. Application of this new model has already contributed to our understanding of granuloma cell traffic, repopulation, and the relationship between systemic immunity and mycobacteria-containing granulomas. The data collected highlight the dynamic interaction between systemic and local immune processes and support a paradigm that defines the granuloma as a highly dynamic structure. Granuloma transplantation also has special potential as a novel latency model that can contribute to our understanding of host protection factors and bacterial mutants, and serve as a platform for drug testing.
结核分枝杆菌感染期间的宿主-病原体生物学极其复杂，尽管研究进展不断加速，但仍了解不足。我们有限的认知阻碍了新药、新一代疫苗和新型疗法的开发。肉芽肿是控制分枝杆菌并使其持续存在的部位，但它仍是宿主-病原体关系中研究最少的方面之一。在此，我们综述了肉芽肿移植新模型的开发、应用、潜在用途及局限性，该模型作为一种工具，用于研究难以探究的特定宿主-病原体相互作用。这一新模型的应用已有助于我们理解肉芽肿细胞运输、再填充以及全身免疫与含分枝杆菌肉芽肿之间的关系。收集到的数据突出了全身和局部免疫过程之间的动态相互作用，并支持一种将肉芽肿定义为高度动态结构的范式。肉芽肿移植作为一种新型潜伏模型也具有特殊潜力，有助于我们理解宿主保护因子和细菌突变体，并作为药物测试的平台。
