美国斯坦福大学医学院Michael Angelo研究组绘制出人类结核肉芽肿的免疫调节图谱。2022年1月20日，《自然—免疫学》杂志在线发表了这项成果。

研究人员使用多路离子束飞行时间成像（MIBI-TOF）对活动性结核病患者组织中的37种蛋白质进行了成像。研究人员构建了一个全面的图谱，并在8个空间微环境中绘制了19个细胞亚群。该图谱显示IFN-γ耗尽的微环境富含TGF-β、调节性T细胞和IDO1⁺ PD-L1⁺骨髓细胞。在对结核病患者外周血的进一步转录组元分析中，免疫调节的趋势反映了肉芽肿成像所确定的趋势。

值得注意的是，PD-L1的表达与进展到活动性结核和治疗反应有关。这些数据表明，在结核病肉芽肿中，存在局部空间协调的免疫调节程序，并具有界定活动性结核的系统性表现。

据悉，人类结核病的特点是在受感染的组织中形成富含免疫力的肉芽肿，其结构和组成被认为会影响疾病的结果。然而，人们对控制人类肉芽肿的空间关系的理解是有限的。

附：英文原文

Title: The immunoregulatory landscape of human tuberculosis granulomas

Author: McCaffrey, Erin F., Donato, Michele, Keren, Leeat, Chen, Zhenghao, Delmastro, Alea, Fitzpatrick, Megan B., Gupta, Sanjana, Greenwald, Noah F., Baranski, Alex, Graf, William, Kumar, Rashmi, Bosse, Marc, Fullaway, Christine Camacho, Ramdial, Pratista K., Forg, Erna, Jojic, Vladimir, Van Valen, David, Mehra, Smriti, Khader, Shabaana A., Bendall, Sean C., van de Rijn, Matt, Kalman, Daniel, Kaushal, Deepak, Hunter, Robert L., Banaei, Niaz, Steyn, Adrie J. C., Khatri, Purvesh, Angelo, Michael

Issue&Volume: 2022-01-20

Abstract: Tuberculosis (TB) in humans is characterized by formation of immune-rich granulomas in infected tissues, the architecture and composition of which are thought to affect disease outcome. However, our understanding of the spatial relationships that control human granulomas is limited. Here, we used multiplexed ion beam imaging by time of flight (MIBI-TOF) to image 37 proteins in tissues from patients with active TB. We constructed a comprehensive atlas that maps 19 cell subsets across 8 spatial microenvironments. This atlas shows an IFN-γ-depleted microenvironment enriched for TGF-β, regulatory T cells and IDO1+ PD-L1+ myeloid cells. In a further transcriptomic meta-analysis of peripheral blood from patients with TB, immunoregulatory trends mirror those identified by granuloma imaging. Notably, PD-L1 expression is associated with progression to active TB and treatment response. These data indicate that in TB granulomas, there are local spatially coordinated immunoregulatory programs with systemic manifestations that define active TB.

DOI: 10.1038/s41590-021-01121-x

Source: https://www.nature.com/articles/s41590-021-01121-x