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解析人类结核病灶的转录组及其临床意义。

Unravelling the transcriptome of the human tuberculosis lesion and its clinical implications.

作者信息

Fonseca Kaori L, Lozano Juan José, Despuig Albert, Habgood-Coote Dominic, Sidorova Julia, Aznar Diego, Arias Lilibeth, Del Río-Álvarez Álvaro, Carrillo-Reixach Juan, Goff Aaron, Wildner Leticia Muraro, Gogishvili Shota, Nikolaishvili Keti, Shubladze Natalia, Avaliani Zaza, Tapia Gustavo, Rodríguez-Martínez Paula, Cardona Pere-Joan, Martinón-Torres Federico, Salas Antonio, Gómez-Carballa Alberto, Armengol Carolina, Waddell Simon J, Kaforou Myrsini, O'Garra Anne, Vashakidze Sergo, Vilaplana Cristina

机构信息

Experimental Tuberculosis Unit (UTE), Fundació Institut Germans Trias i Pujol (IGTP), Badalona, Spain.

Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain.

出版信息

Nat Commun. 2025 May 30;16(1):5028. doi: 10.1038/s41467-025-60255-w.

DOI:10.1038/s41467-025-60255-w
PMID:40447570
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12125219/
Abstract

The tuberculosis (TB) lesion is a complex structure, contributing to the overall spectrum of TB. We characterise, using RNA sequencing, 44 fresh human pulmonary TB lesion samples from 13 TB individuals (drug-sensitive and multidrug-resistant TB) undergoing therapeutic surgery. We confirm clear separation between the TB lesion and adjacent non-lesional tissue, with the lesion samples consistently displaying increased inflammatory profile despite heterogeneity. Using weighted correlation network analysis, we identify 17 transcriptional modules associated with TB lesion and demonstrate a gradient of immune-related transcript abundance according to spatial organization of the lesion. Furthermore, we associate the modular transcriptional signature of the TB lesion with clinical surrogates of treatment efficacy and TB severity. We show that patients with worse disease present an overabundance of immune/inflammation-related modules and downregulated tissue repair and metabolism modules. Our findings provide evidence of a relationship between clinical parameters, treatment response and immune signatures at the infection site.

摘要

肺结核（TB）病灶是一种复杂的结构，对结核病的整体谱系有影响。我们使用RNA测序对13名接受治疗性手术的结核病患者（包括药敏和耐多药结核病患者）的44份新鲜人类肺结核病灶样本进行了特征分析。我们证实了结核病灶与相邻非病灶组织之间的明显分离，尽管存在异质性，但病灶样本始终显示出炎症特征增加。使用加权相关网络分析，我们确定了17个与结核病灶相关的转录模块，并根据病灶的空间组织展示了免疫相关转录本丰度的梯度。此外，我们将结核病灶的模块化转录特征与治疗效果和结核病严重程度的临床替代指标相关联。我们表明，病情较重的患者存在过多的免疫/炎症相关模块以及组织修复和代谢模块下调。我们的研究结果为临床参数、治疗反应和感染部位的免疫特征之间的关系提供了证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/225c/12125219/7d8bec068c1e/41467_2025_60255_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/225c/12125219/d83895a5ffda/41467_2025_60255_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/225c/12125219/565826fa1340/41467_2025_60255_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/225c/12125219/93fb504b8d06/41467_2025_60255_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/225c/12125219/2b9e8ca99848/41467_2025_60255_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/225c/12125219/2291e49b242b/41467_2025_60255_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/225c/12125219/7d8bec068c1e/41467_2025_60255_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/225c/12125219/d83895a5ffda/41467_2025_60255_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/225c/12125219/565826fa1340/41467_2025_60255_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/225c/12125219/93fb504b8d06/41467_2025_60255_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/225c/12125219/2b9e8ca99848/41467_2025_60255_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/225c/12125219/2291e49b242b/41467_2025_60255_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/225c/12125219/7d8bec068c1e/41467_2025_60255_Fig6_HTML.jpg

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Immune mapping of human tuberculosis and sarcoidosis lung granulomas.人类肺结核和结节病肺部肉芽肿的免疫图谱。
Front Immunol. 2024 Feb 7;14:1332733. doi: 10.3389/fimmu.2023.1332733. eCollection 2023.
3
The Association of Novel Single-Nucleotide Variants in the Collagen Matrix-Encoding Gene with Aortic Aneurysmal Disease.
感染非人灵长类动物肉芽肿内巨噬细胞多样性的空间特异性编程。
bioRxiv. 2025 Jun 17:2025.06.12.659348. doi: 10.1101/2025.06.12.659348.
胶原蛋白基质编码基因中的新型单核苷酸变异与主动脉瘤疾病的关联
Life (Basel). 2023 Jul 28;13(8):1649. doi: 10.3390/life13081649.
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Antigen-specific B cells direct T follicular-like helper cells into lymphoid follicles to mediate Mycobacterium tuberculosis control.抗原特异性 B 细胞引导滤泡辅助性 T 细胞进入淋巴滤泡，从而介导对结核分枝杆菌的控制。
Nat Immunol. 2023 May;24(5):855-868. doi: 10.1038/s41590-023-01476-3. Epub 2023 Apr 3.
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