Transcriptional profile of Mycobacterium tuberculosis infection in people living with HIV.

IF 4.6 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES iScience Pub Date : 2024-10-21 eCollection Date: 2024-11-15 DOI:10.1016/j.isci.2024.111228

Burcu Tepekule, Lisa Jörimann, Corinne D Schenkel, Lennart Opitz, Jasmin Tschumi, Rebekka Wolfensberger, Kathrin Neumann, Katharina Kusejko, Marius Zeeb, Lucas Boeck, Marisa Kälin, Julia Notter, Hansjakob Furrer, Matthias Hoffmann, Hans H Hirsch, Alexandra Calmy, Matthias Cavassini, Niklaus D Labhardt, Enos Bernasconi, Gabriela Oesch, Karin J Metzner, Dominique L Braun, Huldrych F Günthard, Roger D Kouyos, Fergal Duffy, Johannes Nemeth

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Abstract

In people with HIV-1 (PWH), Mycobacterium tuberculosis (MTB) infection poses a significant threat. While active tuberculosis (TB) accelerates immunodeficiency, the interaction between MTB and HIV-1 during asymptomatic phases remains unclear. Analysis of peripheral blood mononuclear cells (PBMC) transcriptomic profiles in PWH, with and without controlled viral loads, revealed distinct clustering in MTB-infected individuals. Functional annotation identified alterations in IL-6, TNF, and KRAS pathways. Notably, MTB-related genes displayed an inverse correlation with HIV-1 viremia, at both individual and signature score levels. These findings suggest that MTB infection in PWH induces a shift in immune system activation, inversely related to HIV-1 viral load. These results may explain the observed enhanced antiretroviral control in MTB-infected PWH. This study highlights the complex interplay between MTB and HIV-1, emphasizing the importance of understanding their interaction for managing co-infections in this population.

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艾滋病病毒感染者感染结核分枝杆菌的转录谱。

在 HIV-1 感染者（PWH）中，结核分枝杆菌（MTB）感染构成了重大威胁。虽然活动性结核病（TB）会加速免疫缺陷，但在无症状阶段，MTB 与 HIV-1 之间的相互作用仍不清楚。对感染和未感染病毒载量受控的肺结核患者外周血单核细胞（PBMC）转录组的分析显示，MTB 感染者有明显的聚集现象。功能注释发现了 IL-6、TNF 和 KRAS 通路的改变。值得注意的是，在个体和特征得分水平上，MTB 相关基因与 HIV-1 病毒血症呈反相关。这些研究结果表明，PWH 感染 MTB 会诱导免疫系统激活的转变，而这种转变与 HIV-1 病毒载量成反比。这些结果可能解释了在 MTB 感染的 PWH 中观察到的抗逆转录病毒控制增强的原因。这项研究凸显了 MTB 和 HIV-1 之间复杂的相互作用，强调了了解它们之间的相互作用对控制这类人群合并感染的重要性。

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来源期刊

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

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