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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., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

This data article presents datasets associated with the research article entitled "The immunological architecture of granulomatous inflammation in central nervous system tuberculosis'' (Zaharie et al., 2020). The morphology of tuberculosis related granulomas within the central nervous system of human patients was visualized in six different three-dimensional (3D) models. Post-mortem, formalin fixed and paraffin embedded specimens from deceased tuberculous meningitis patients were immunohistochemically stained and 800 serial histologically stained sections were acquired. Images from all sections were obtained with an Olympus BX43 light microscope and structures were identified, labeled and made three-dimensional. The interactive 3D-models allows the user to directly visualize the morphology of the granulomas and to understand the localization of the granulomas. The 3D-models can be used for multiple purposes and provide both an educational source as a gold standard for further animal studies, human research and the development of in silico models on the topic of central nervous system tuberculosis., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships which have, or could be perceived to have, influenced the work reported in this article., (© 2020 The Author(s).)