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The gut microbiota mediates protective immunity against tuberculosis via modulation of lncRNA

The gut-lung axis has been implicated as a potential therapeutic target in lung disorders. While increasing evidence suggests that gut microbiota plays a critical role in regulating host immunity and contributing to tuberculosis (TB) development and progression, the underlying mechanisms whereby gut...

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Autores principales: Yang, Fang, Yang, Yi, Chen, Lingming, Zhang, Zhiyi, Liu, Linna, Zhang, Chunmin, Mai, Qiongdan, Chen, Yiwei, Chen, Zixu, Lin, Tao, Chen, Liang, Guo, Huixin, Zhou, Lin, Shen, Hongbo, Chen, Xinchun, Liu, Lei, Zhang, Guoliang, Liao, Hongying, Zeng, Lingchan, Zeng, Gucheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8966992/
https://www.ncbi.nlm.nih.gov/pubmed/35343370
http://dx.doi.org/10.1080/19490976.2022.2029997
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author Yang, Fang
Yang, Yi
Chen, Lingming
Zhang, Zhiyi
Liu, Linna
Zhang, Chunmin
Mai, Qiongdan
Chen, Yiwei
Chen, Zixu
Lin, Tao
Chen, Liang
Guo, Huixin
Zhou, Lin
Shen, Hongbo
Chen, Xinchun
Liu, Lei
Zhang, Guoliang
Liao, Hongying
Zeng, Lingchan
Zeng, Gucheng
author_facet Yang, Fang
Yang, Yi
Chen, Lingming
Zhang, Zhiyi
Liu, Linna
Zhang, Chunmin
Mai, Qiongdan
Chen, Yiwei
Chen, Zixu
Lin, Tao
Chen, Liang
Guo, Huixin
Zhou, Lin
Shen, Hongbo
Chen, Xinchun
Liu, Lei
Zhang, Guoliang
Liao, Hongying
Zeng, Lingchan
Zeng, Gucheng
author_sort Yang, Fang
collection PubMed
description The gut-lung axis has been implicated as a potential therapeutic target in lung disorders. While increasing evidence suggests that gut microbiota plays a critical role in regulating host immunity and contributing to tuberculosis (TB) development and progression, the underlying mechanisms whereby gut microbiota may impact TB outcomes are not fully understood. Here, we found that broad-spectrum antibiotics treatment increased susceptibility to Mycobacterium tuberculosis (M. tuberculosis) infection and modulated pulmonary inflammatory responses in mouse M. tuberculosis infection model. We then identified a commensal gut bacteria-regulated lncRNA, termed lncRNA-CGB, which was down-regulated by dysbiosis of gut microbiota during TB infection. Furthermore, we found that Bacteroides fragilis (B. fragilis) was a direct regulator of lncRNA-CGB, and oral administration of B. fragilis enhanced expression of lncRNA-CGB and promoted anti-TB immunity. Genomic knock-out of lncRNA-CGB led to reduced IFN-γ expression and impaired anti-TB immunity, therefore leading to detrimental effects on M. tuberculosis infection. Mechanistically, lncRNA-CGB interacted with EZH2 and negatively regulated H3K27 tri-methylation (H3K27Me3) epigenetic programming, leading to enhanced IFN-γ expression. Thus, this work not only uncovered previously unrecognized importance of gut bacteria-lncRNA-EZH2-H3K27Me3 axis in conferring immune protection against TB but also identified a potential new paradigm to develop a microbiota-based treatment against TB and potentially other diseases.
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spelling pubmed-89669922022-03-31 The gut microbiota mediates protective immunity against tuberculosis via modulation of lncRNA Yang, Fang Yang, Yi Chen, Lingming Zhang, Zhiyi Liu, Linna Zhang, Chunmin Mai, Qiongdan Chen, Yiwei Chen, Zixu Lin, Tao Chen, Liang Guo, Huixin Zhou, Lin Shen, Hongbo Chen, Xinchun Liu, Lei Zhang, Guoliang Liao, Hongying Zeng, Lingchan Zeng, Gucheng Gut Microbes Research Paper The gut-lung axis has been implicated as a potential therapeutic target in lung disorders. While increasing evidence suggests that gut microbiota plays a critical role in regulating host immunity and contributing to tuberculosis (TB) development and progression, the underlying mechanisms whereby gut microbiota may impact TB outcomes are not fully understood. Here, we found that broad-spectrum antibiotics treatment increased susceptibility to Mycobacterium tuberculosis (M. tuberculosis) infection and modulated pulmonary inflammatory responses in mouse M. tuberculosis infection model. We then identified a commensal gut bacteria-regulated lncRNA, termed lncRNA-CGB, which was down-regulated by dysbiosis of gut microbiota during TB infection. Furthermore, we found that Bacteroides fragilis (B. fragilis) was a direct regulator of lncRNA-CGB, and oral administration of B. fragilis enhanced expression of lncRNA-CGB and promoted anti-TB immunity. Genomic knock-out of lncRNA-CGB led to reduced IFN-γ expression and impaired anti-TB immunity, therefore leading to detrimental effects on M. tuberculosis infection. Mechanistically, lncRNA-CGB interacted with EZH2 and negatively regulated H3K27 tri-methylation (H3K27Me3) epigenetic programming, leading to enhanced IFN-γ expression. Thus, this work not only uncovered previously unrecognized importance of gut bacteria-lncRNA-EZH2-H3K27Me3 axis in conferring immune protection against TB but also identified a potential new paradigm to develop a microbiota-based treatment against TB and potentially other diseases. Taylor & Francis 2022-03-28 /pmc/articles/PMC8966992/ /pubmed/35343370 http://dx.doi.org/10.1080/19490976.2022.2029997 Text en © 2022 The Author(s). Published with license by Taylor & Francis Group, LLC. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Paper
Yang, Fang
Yang, Yi
Chen, Lingming
Zhang, Zhiyi
Liu, Linna
Zhang, Chunmin
Mai, Qiongdan
Chen, Yiwei
Chen, Zixu
Lin, Tao
Chen, Liang
Guo, Huixin
Zhou, Lin
Shen, Hongbo
Chen, Xinchun
Liu, Lei
Zhang, Guoliang
Liao, Hongying
Zeng, Lingchan
Zeng, Gucheng
The gut microbiota mediates protective immunity against tuberculosis via modulation of lncRNA
title The gut microbiota mediates protective immunity against tuberculosis via modulation of lncRNA
title_full The gut microbiota mediates protective immunity against tuberculosis via modulation of lncRNA
title_fullStr The gut microbiota mediates protective immunity against tuberculosis via modulation of lncRNA
title_full_unstemmed The gut microbiota mediates protective immunity against tuberculosis via modulation of lncRNA
title_short The gut microbiota mediates protective immunity against tuberculosis via modulation of lncRNA
title_sort gut microbiota mediates protective immunity against tuberculosis via modulation of lncrna
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8966992/
https://www.ncbi.nlm.nih.gov/pubmed/35343370
http://dx.doi.org/10.1080/19490976.2022.2029997
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