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人结核病防卫和发病机制的潜在特征
作者:小柯机器人 发布时间:2020/3/17 15:26:55

英国弗朗西斯•克里克研究所Anne O’Garra和Lúcia Moreira-Teixeira小组在研究中取得进展。他们利用小鼠转录组揭示了人类结核病(TB)防卫和发病机制的潜在特征。3月16日,论文在线发表在《自然-免疫学》上。

研究人员发现感染结核分枝杆菌临床分离株的易感小鼠血液转录特征与活跃的人类结核病的类似,具有I型干扰素应答、中性粒细胞活化和募集以及B淋巴细胞、自然杀伤和T细胞效应反应的丢失。

另外,抗性但非易感的小鼠在感染后,其肺显示出肺B细胞、自然杀伤和T细胞效应反应增加。

值得注意的是,在潜伏性结核病进展前,小鼠和人类共有的活性疾病血液特征也很明显。这些数据表明这些反应可以预测并有助于解释进行性结核分枝杆菌感染的发病机理。

据悉,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,但它们在揭示决定人类结核病耐药性和疾病进展有效因素方面一直广受争议。

附:英文原文

Title: Mouse transcriptome reveals potential signatures of protection and pathogenesis in human tuberculosis

Author: Lcia Moreira-Teixeira, Olivier Tabone, Christine M. Graham, Akul Singhania, Evangelos Stavropoulos, Paul S. Redford, Probir Chakravarty, Simon L. Priestnall, Alejandro Suarez-Bonnet, Eleanor Herbert, Katrin D. Mayer-Barber, Alan Sher, Kaori L. Fonseca, Jeremy Sousa, Baltazar C, Raman Verma, Pranabashis Haldar, Margarida Saraiva, Anne OGarra

Issue&Volume: 2020-03-16

Abstract: 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.

DOI: 10.1038/s41590-020-0610-z

Source: https://www.nature.com/articles/s41590-020-0610-z

期刊信息

Nature Immunology:《自然—免疫学》,创刊于2000年。隶属于施普林格·自然出版集团,最新IF:23.53
官方网址:https://www.nature.com/ni/
投稿链接:https://mts-ni.nature.com/cgi-bin/main.plex