Mouse transcriptome reveals potential signatures of protection and pathogenesis in human tuberculosis.,Nature Immunology

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Mouse transcriptome reveals potential signatures of protection and pathogenesis in human tuberculosis.
Nature Immunology ( IF 27.7 ) Pub Date : 2020-03-16 , DOI: 10.1038/s41590-020-0610-z
Lúcia Moreira-Teixeira ₁ , Olivier Tabone ₁ , Christine M Graham ₁ , Akul Singhania ₁ , Evangelos Stavropoulos ₁ , Paul S Redford _{1,

2} , Probir Chakravarty ₃ , Simon L Priestnall _{4,

5} , Alejandro Suarez-Bonnet _{4,

5} , Eleanor Herbert _{4,

5} , Katrin D Mayer-Barber ₆ , Alan Sher ₇ , Kaori L Fonseca _{8,

9,

10,

11} , Jeremy Sousa _{8,

9,

10} , Baltazar Cá _{8,

9,

10,

11} , Raman Verma ₁₂ , Pranabashis Haldar ₁₂ , Margarida Saraiva _{8,

9} , Anne O'Garra _{1,

13}

Affiliation

Laboratory of Immunoregulation and Infection, The Francis Crick Institute, London, UK.
GSK R&D, Medicines Research Centre, Stevenage, UK.
Bioinformatics Core, The Francis Crick Institute, London, UK.
Department of Pathobiology & Population Sciences, Royal Veterinary College, London, UK.
Experimental Histopathology Team, The Francis Crick Institute, London, UK.
Inflammation and Innate Immunity Unit, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.
IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal.
ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal.
Programa de Pós-Graduação Ciência para o Desenvolvimento (PGCD), Instituto Gulbenkian de Ciência (IGC), Oeiras, Portugal.
Department of Respiratory Sciences, National Institute for Health Research Respiratory Biomedical Research Centre, University of Leicester, Leicester, UK.
National Heart and Lung Institute, Imperial College London, London, UK.

Although mouse infection models have been extensively used to study the host response to Mycobacterium tuberculosis, their validity in revealing determinants of human tuberculosis (TB) resistance and disease progression has been heavily debated. Here, we show that the modular transcriptional signature in the blood of susceptible mice infected with a clinical isolate of M. tuberculosis resembles that of active human TB disease, with dominance of a type I interferon response and neutrophil activation and recruitment, together with a loss in B lymphocyte, natural killer and T cell effector responses. In addition, resistant but not susceptible strains of mice show increased lung B cell, natural killer and T cell effector responses in the lung upon infection. Notably, the blood signature of active disease shared by mice and humans is also evident in latent TB progressors before diagnosis, suggesting that these responses both predict and contribute to the pathogenesis of progressive M. tuberculosis infection.

中文翻译：

小鼠转录组揭示了人类结核病的保护和发病机制的潜在特征。

尽管小鼠感染模型已被广泛用于研究宿主对结核分枝杆菌的反应，但其在揭示人类结核病 (TB) 耐药性和疾病进展决定因素方面的有效性一直存在激烈争议。在这里，我们表明，感染结核分枝杆菌临床分离株的易感小鼠血液中的模块化转录特征与活动性人类结核病的特征相似，以 I 型干扰素反应和中性粒细胞激活和募集为主，同时缺失B 淋巴细胞、自然杀伤细胞和 T 细胞效应反应。此外，耐药但非易感品系的小鼠在感染后，肺部 B 细胞、自然杀伤细胞和 T 细胞效应反应增加。值得注意的是，小鼠和人类共有的活动性疾病的血液特征在诊断前的潜伏结核进展者中也很明显，这表明这些反应既可以预测也有助于进行性结核分枝杆菌感染的发病机制。

更新日期：2020-04-24

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