Of all tuberculosis (TB) cases, 1% affects the central nervous system (CNS), with a mortality rate of up to 60%. Our aim is to fill the 'key gap' in TBM research by analyzing brain specimens in a unique historical cohort of 84 patients, focusing on granuloma formation. We describe three different types: non-necrotizing, necrotizing gummatous, and necrotizing abscess type granuloma. Our hypothesis is that these different types of granuloma are developmental stages of the same pathological process. All types were present in each patient and were mainly localized in the leptomeninges. Intra-parenchymal granulomas were less abundant than the leptomeningeal ones and mainly located close to the cerebrospinal fluid (subpial and subependymal). We found that most of the intraparenchymal granulomas are an extension of leptomeningeal lesions which is the opposite of the classical Rich focus theory. We present a 3D-model to facilitate further understanding of the topographic relation of granulomas with leptomeninges, brain parenchyma and blood vessels. We describe innate and adaptive immune responses during granuloma formation including the cytokine profiles. We emphasize the presence of leptomeningeal B-cell aggregates as tertiary lymphoid structures. Our study forms a basis for further research in neuroinflammation and infectious diseases of the CNS, especially TB.

中文翻译：

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中枢神经系统结核肉芽肿性炎症的免疫结构

在所有结核病 (TB) 病例中，1% 会影响中枢神经系统 (CNS)，死亡率高达 60%。我们的目标是通过分析 84 名患者的独特历史队列中的脑标本来填补 TBM 研究中的“关键空白”，重点是肉芽肿的形成。我们描述了三种不同的类型：非坏死性、坏死性胶质瘤和坏死性脓肿型肉芽肿。我们的假设是这些不同类型的肉芽肿是同一病理过程的发育阶段。所有类型都存在于每位患者中，并且主要位于软脑膜中。实质内肉芽肿不如软脑膜肉芽肿多，主要位于靠近脑脊液（软脑膜下和室管膜下）。我们发现大部分实质内肉芽肿是软脑膜病变的延伸，这与经典的 Rich 病灶理论相反。我们提出了一个 3D 模型，以促进进一步了解肉芽肿与软脑膜、脑实质和血管的地形关系。我们描述了肉芽肿形成过程中的先天性和适应性免疫反应，包括细胞因子谱。我们强调软脑膜 B 细胞聚集体作为三级淋巴结构的存在。我们的研究为进一步研究中枢神经系统的神经炎症和传染病，尤其是结核病奠定了基础。我们描述了肉芽肿形成过程中的先天性和适应性免疫反应，包括细胞因子谱。我们强调软脑膜 B 细胞聚集体作为三级淋巴结构的存在。我们的研究为进一步研究中枢神经系统的神经炎症和传染病，尤其是结核病奠定了基础。我们描述了肉芽肿形成过程中的先天性和适应性免疫反应，包括细胞因子谱。我们强调软脑膜 B 细胞聚集体作为三级淋巴结构的存在。我们的研究为进一步研究中枢神经系统的神经炎症和传染病，尤其是结核病奠定了基础。