Krueger Gesa, Faisal Shah, Dorhoi Anca
Institute of Immunology, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Greifswald, Germany.
Institute of Medical Biochemistry and Molecular Biology, University Medicine Greifswald, Greifswald, Germany.
Front Immunol. 2025 Mar 24;16:1575133. doi: 10.3389/fimmu.2025.1575133. eCollection 2025.
The hallmark tissue lesions of tuberculosis (TB) are granulomas. These multicellular structures exhibit varying degrees of cellular complexity, are dynamic, and show considerable diversity within and between hosts. Categorization based on gross pathologic features, particularly caseation and necrosis, was historically coined prior to the identification of mycobacteria as the causative agent of TB. More recently, granuloma zonation based on immune cell composition, metabolite abundance, and physical characteristics has gained attention. With the advent of single-cell analyses, distinct microenvironments and cellular ecosystems within TB granulomas have been identified. We summarize the architecture of TB granulomas and highlight their cellular heterogeneity, including cell niches as well as physical factors such as oxygen gradients that modulate lesion fate. We discuss opportunities for therapy, highlighting new models and the power of modeling to unravel granuloma features and trajectories. Understanding the relevance of the granuloma microenvironment to disease pathophysiology will facilitate the development of more effective interventions, such as host-directed therapies for TB.
结核病（TB）的标志性组织病变是肉芽肿。这些多细胞结构表现出不同程度的细胞复杂性，具有动态性，并且在宿主内部和宿主之间表现出相当大的多样性。基于大体病理特征，特别是干酪样坏死和坏死进行的分类，在分枝杆菌被确认为结核病病原体之前就已存在。最近，基于免疫细胞组成、代谢物丰度和物理特征的肉芽肿分区受到了关注。随着单细胞分析的出现，已确定了结核肉芽肿内不同的微环境和细胞生态系统。我们总结了结核肉芽肿的结构，并强调了它们的细胞异质性，包括细胞龛以及调节病变命运的物理因素，如氧梯度。我们讨论了治疗机会，重点介绍了新模型以及建模在揭示肉芽肿特征和发展轨迹方面的作用。了解肉芽肿微环境与疾病病理生理学的相关性将有助于开发更有效的干预措施，如针对结核病的宿主导向疗法。
