Dual RNA Sequencing of Mycobacterium tuberculosis-Infected Human Splenic Macrophages Reveals a Strain-Dependent Host-Pathogen Response to Infection.

Dual RNA Sequencing of Mycobacterium tuberculosis-Infected Human Splenic Macrophages Reveals a Strain-Dependent Host-Pathogen Response to Infection.
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DOI:
10.3390/ijms23031803
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发表时间:
2022-02-04
影响因子:
5.6
通讯作者:
Barrera LF
Barrera LF
中科院分区:
生物学2区
文献类型:
--
作者:
López-Agudelo VA;Baena A;Barrera V;Cabarcas F;Alzate JF;Beste DJV;Ríos-Estepa R;Barrera LF

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结核病 (TB) 是由结核分枝杆菌 (Mtb) 引起的,可导致肺结核和肺外结核,从而使 Mtb 播散到许多其他器官和组织。传播发生在疾病早期,细菌首先出现在邻近肺部的淋巴结中,然后出现在肺外器官(包括脾脏)中。人类组织巨噬细胞和结核分枝杆菌细胞内临床分离株的早期整体基因表达反应的研究很少。使用双 RNA 测序,我们探索了受感染的人脾巨噬细胞 (hSM) 中两种密切相关的拉丁美洲和地中海 (LAM) 结核分枝杆菌家族临床菌株的 mRNA 谱。这项工作表明,尽管这些病原体具有遗传相似性,但它们仍介导独特的宿主反应。使用基因组规模的宿主-病原体代谢重建来进一步分析数据,我们强调感染 Mtb 菌株也决定了宿主和病原体的代谢反应。因此,巨噬细胞个体发育和结核分枝杆菌的遗传衍生程序指导宿主与病原体的相互作用。
Tuberculosis (TB) is caused by Mycobacterium tuberculosis (Mtb), leading to pulmonary and extrapulmonary TB, whereby Mtb is disseminated to many other organs and tissues. Dissemination occurs early during the disease, and bacteria can be found first in the lymph nodes adjacent to the lungs and then later in the extrapulmonary organs, including the spleen. The early global gene expression response of human tissue macrophages and intracellular clinical isolates of Mtb has been poorly studied. Using dual RNA-seq, we have explored the mRNA profiles of two closely related clinical strains of the Latin American and Mediterranean (LAM) family of Mtb in infected human splenic macrophages (hSMs). This work shows that these pathogens mediate a distinct host response despite their genetic similarity. Using a genome-scale host–pathogen metabolic reconstruction to analyze the data further, we highlight that the infecting Mtb strain also determines the metabolic response of both the host and pathogen. Thus, macrophage ontogeny and the genetic-derived program of Mtb direct the host–pathogen interaction.
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