近日，美国斯坦福大学医学院教授Michael Angelo团队的最新研究提出了结核肉芽肿细胞组织和细菌控制的免疫代谢图谱。2026年2月23日出版的《自然—免疫学》杂志发表了这项成果。

在这里，该研究组确定了建立这种耐受性生态位的候选驱动因素，并表明这种反应的强度与细菌持久性相关。该课题组研究人员对16例感染低剂量Mtb 9-12周的非人灵长类动物的52个肉芽肿进行了多模式空间分析。每个肉芽肿的细菌负荷被单独量化，使他们能够评估肉芽肿的空间结构和功能与感染控制的关系。

课题组人员发现结核肉芽肿的一个普遍特征是骨髓核心分裂成两个不同的代谢环境，其中一个是缺氧的。这种缺氧环境与病理性免疫细胞状态、肉芽肿的功能失调细胞组织以及淋巴细胞浸润的几乎完全阻断有关，这是成功的宿主反应所必需的。这些缺氧相关特征的程度与较高的细菌负荷相关。该团队得出结论，缺氧与肉芽肿内的免疫细胞状态和组织有关，并可能破坏对结核病的免疫。

据悉，尽管免疫细胞大量浸润，但结核（TB）肉芽肿常常破坏宿主对结核分枝杆菌（Mtb）感染的反应，并支持细菌的持续存在。人结核肉芽肿富含通常与肿瘤免疫逃避相关的免疫抑制因子，提高了它们促进对感染耐受的可能性。

附：英文原文

Title: The immunometabolic topography of cellular organization and bacterial control in tuberculosis granulomas

Author: McCaffrey, Erin F., Delmastro, Alea C., Fitzhugh, Isobel, Ranek, Jolene S., Douglas, Sarah, Peters, Joshua M., Fullaway, Christine Camacho, Bosse, Marc, Liu, Candace C., Gillen, Craig, Greenwald, Noah F., Anzick, Sarah, Martens, Craig, Winfree, Seth, Bai, Yunhao, Sowers, Cameron, Goldston, Mako, Kong, Alex, Boonrat, Potchara, Bigbee, Carolyn L., Venugopalan, Roopa, Maiello, Pauline, Klein, Edwin, Rodgers, Mark A., Scanga, Charles A., Lin, Philana Ling, Bendall, Sean C., Kirschner, Denise E., Fortune, Sarah M., Bryson, Bryan D., Butler, J. Russell, Mattila, Joshua T., Flynn, JoAnne L., Angelo, Michael

Issue&Volume: 2026-02-23

Abstract: Despite being heavily infiltrated by immune cells, tuberculosis (TB) granulomas often subvert the host response to Mycobacterium tuberculosis (Mtb) infection and support bacterial persistence. Human TB granulomas are enriched for immunosuppressive factors typically associated with tumor-immune evasion, raising the possibility that they promote tolerance to infection. Here we identify candidate drivers for establishing this tolerogenic niche and show that the magnitude of this response correlates with bacterial persistence. We conducted a multimodal spatial analysis of 52 granulomas from 16 nonhuman primates infected with low-dose Mtb for 9–12 weeks. Each granuloma’s bacterial burden was quantified individually, enabling us to assess how granuloma spatial structure and function relate to infection control. We found that a universal feature of TB granulomas is partitioning of the myeloid core into two distinct metabolic environments, one of which is hypoxic. This hypoxic environment is associated with pathological immune cell states, dysfunctional cellular organization of the granuloma, and a near-complete blockade of lymphocyte infiltration that would be required for a successful host response. The extent of these hypoxia-associated features correlates with higher bacterial burden. We conclude that hypoxia correlates with immune cell state and organization within granulomas and might subvert immunity to TB.

DOI: 10.1038/s41590-026-02431-8

Source: https://www.nature.com/articles/s41590-026-02431-8