小柯机器人

美国麻省理工学院Alex K. Shalek等研究人员合作利用猕猴肺部肉芽肿的多模态分析揭示结核病控制的细胞相关因素。相关论文于2022年4月27日在线发表在《免疫》杂志上。

研究人员通过对纵向正电子发射断层扫描和计算机断层扫描成像、单细胞RNA测序和细菌清除的测量进行联合登记，确定了猕猴肺部肉芽肿中细菌控制的相关因素。细菌持续存在于肥大细胞、内皮细胞、成纤维细胞和浆细胞富集的肉芽肿中，它们之间通过2型免疫和伤口愈合途径进行信号传递。推动细菌控制的肉芽肿的特点是细胞生态系统富含1-17型、干型和细胞毒性T细胞，参与到涉及不同细胞群的促炎症信号网络中。

在感染后期出现的肉芽肿显示出限制性肉芽肿的功能特征，并且更有能力杀死结核分枝杆菌。这些结果定义了复杂的多细胞生态系统，它是肉芽肿解决的基础，并突出了可用于开发新的结核病疫苗和治疗策略的宿主免疫靶标。

据了解，结核分枝杆菌的肺部感染导致一个复杂的多细胞结构：肉芽肿。在一些肉芽肿中，免疫活动促进了细菌的清除，但在其他肉芽肿中，细菌持续存在并生长。

附：英文原文

Title: Multimodal profiling of lung granulomas in macaques reveals cellular correlates of tuberculosis control

Author: Hannah P. Gideon, Travis K. Hughes, Constantine N. Tzouanas, Marc H. Wadsworth, Ang Andy Tu, Todd M. Gierahn, Joshua M. Peters, Forrest F. Hopkins, Jun-Rong Wei, Conner Kummerlowe, Nicole L. Grant, Kievershen Nargan, Jia Yao Phuah, H. Jacob Borish, Pauline Maiello, Alexander G. White, Caylin G. Winchell, Sarah K. Nyquist, Sharie Keanne C. Ganchua, Amy Myers, Kush V. Patel, Cassaundra L. Ameel, Catherine T. Cochran, Samira Ibrahim, Jaime A. Tomko, Lonnie James Frye, Jacob M. Rosenberg, Angela Shih, Michael Chao, Edwin Klein, Charles A. Scanga, Jose Ordovas-Montanes, Bonnie Berger, Joshua T. Mattila, Rajhmun Madansein, J. Christopher Love, Philana Ling Lin, Alasdair Leslie, Samuel M. Behar, Bryan Bryson, JoAnne L. Flynn, Sarah M. Fortune, Alex K. Shalek

Issue&Volume: 2022-04-27

Abstract: Mycobacterium tuberculosis lung infection results in a complex multicellular structure: the granuloma. In some granulomas, immune activity promotes bacterial clearance, but in others, bacteria persist and grow. We identified correlates of bacterial control in cynomolgus macaque lung granulomas by co-registering longitudinal positron emission tomography and computed tomography imaging, single-cell RNA sequencing, and measures of bacterial clearance. Bacterial persistence occurred in granulomas enriched for mast, endothelial, fibroblast, and plasma cells, signaling amongst themselves via type 2 immunity and wound-healing pathways. Granulomas that drove bacterial control were characterized by cellular ecosystems enriched for type 1-type 17, stem-like, and cytotoxic T cells engaged in pro-inflammatory signaling networks involving diverse cell populations. Granulomas that arose later in infection displayed functional characteristics of restrictive granulomas and were more capable of killing Mtb. Our results define the complex multicellular ecosystems underlying (lack of) granuloma resolution and highlight host immune targets that can be leveraged to develop new vaccine and therapeutic strategies for TB.

DOI: 10.1016/j.immuni.2022.04.004

Source: https://www.cell.com/immunity/fulltext/S1074-7613(22)00175-3

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