Soluble immune mediators orchestrate protective in vitro granulomatous responses across Mycobacterium tuberculosis complex lineages.

IF 6.4 1区 生物学 Q1 BIOLOGY
eLife Pub Date : 2025-03-31 DOI:10.7554/eLife.99062
Ainhoa Arbués, Sarah Schmidiger, Miriam Reinhard, Sonia Borrell, Sebastien Gagneux, Damien Portevin
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引用次数: 0

Abstract

The members of the Mycobacterium tuberculosis complex (MTBC) causing human tuberculosis comprise 10 phylogenetic lineages that differ in their geographical distribution. The human consequences of this phylogenetic diversity remain poorly understood. Here, we assessed the phenotypic properties at the host-pathogen interface of 14 clinical strains representing five major MTBC lineages. Using a human in vitro granuloma model combined with bacterial load assessment, microscopy, flow cytometry, and multiplexed-bead arrays, we observed considerable intra-lineage diversity. Yet, modern lineages were overall associated with increased growth rate and more pronounced granulomatous responses. MTBC lineages exhibited distinct propensities to accumulate triglyceride lipid droplets-a phenotype associated with dormancy-that was particularly pronounced in lineage 2 and reduced in lineage 3 strains. The most favorable granuloma responses were associated with strong CD4 and CD8 T cell activation as well as inflammatory responses mediated by CXCL9, granzyme B, and TNF. Both of which showed consistent negative correlation with bacterial proliferation across genetically distant MTBC strains of different lineages. Taken together, our data indicate that different virulence strategies and protective immune traits associate with MTBC genetic diversity at lineage and strain level.

可溶性免疫介质协调跨结核分枝杆菌复杂谱系的保护性体外肉芽肿反应。
引起人类结核病的结核分枝杆菌复合体(MTBC)的成员包括10个不同地理分布的系统发育谱系。人类对这种系统发育多样性的影响仍然知之甚少。在这里,我们评估了代表5个主要MTBC谱系的14个临床菌株在宿主-病原体界面的表型特性。利用人体外肉芽肿模型,结合细菌负荷评估、显微镜、流式细胞术和多路头阵列,我们观察到相当大的谱系内多样性。然而,现代谱系总体上与增加的生长速率和更明显的肉芽肿反应有关。MTBC谱系表现出明显的甘油三酯脂滴积聚倾向,这是一种与休眠相关的表型,在谱系2中尤为明显,而在谱系3中则有所减少。最有利的肉芽肿反应与强烈的CD4和CD8 T细胞活化以及CXCL9、颗粒酶B和TNF介导的炎症反应有关。两者均与不同谱系的遗传距离较远的MTBC菌株的细菌增殖呈一致的负相关。综上所述,我们的数据表明,不同的毒力策略和保护性免疫性状与MTBC在谱系和品系水平上的遗传多样性有关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
eLife
eLife BIOLOGY-
CiteScore
12.90
自引率
3.90%
发文量
3122
审稿时长
17 weeks
期刊介绍: eLife is a distinguished, not-for-profit, peer-reviewed open access scientific journal that specializes in the fields of biomedical and life sciences. eLife is known for its selective publication process, which includes a variety of article types such as: Research Articles: Detailed reports of original research findings. Short Reports: Concise presentations of significant findings that do not warrant a full-length research article. Tools and Resources: Descriptions of new tools, technologies, or resources that facilitate scientific research. Research Advances: Brief reports on significant scientific advancements that have immediate implications for the field. Scientific Correspondence: Short communications that comment on or provide additional information related to published articles. Review Articles: Comprehensive overviews of a specific topic or field within the life sciences.
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