Allele-specific induction of IL-1β expression by C/EBPβ and PU.1 contributes to increased tuberculosis susceptibility.
Mycobacterium tuberculosis infection is associated with a spectrum of clinical outcomes, from long-term latent infection to different manifestations of progressive disease. Pro-inflammatory pathways, such as those controlled by IL-1β, have the contrasting potential both to prevent disease by restric...
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oai:doaj.org-article:c07c38f68028461ea230f61001158d032021-11-25T05:45:55ZAllele-specific induction of IL-1β expression by C/EBPβ and PU.1 contributes to increased tuberculosis susceptibility.1553-73661553-737410.1371/journal.ppat.1004426https://doaj.org/article/c07c38f68028461ea230f61001158d032014-10-01T00:00:00Zhttps://doi.org/10.1371/journal.ppat.1004426https://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Mycobacterium tuberculosis infection is associated with a spectrum of clinical outcomes, from long-term latent infection to different manifestations of progressive disease. Pro-inflammatory pathways, such as those controlled by IL-1β, have the contrasting potential both to prevent disease by restricting bacterial replication, and to promote disease by inflicting tissue damage. Thus, the ultimate contribution of individual inflammatory pathways to the outcome of M. tuberculosis infection remains ambiguous. In this study, we identified a naturally-occurring polymorphism in the human IL1B promoter region, which alters the association of the C/EBPβ and PU.1 transcription factors and controls Mtb-induced IL-1β production. The high-IL-1β expressing genotype was associated with the development of active tuberculosis, the severity of pulmonary disease and poor treatment outcome in TB patients. Higher IL-1β expression did not suppress the activity of IFN-γ-producing T cells, but instead correlated with neutrophil accumulation in the lung. These observations support a specific role for IL-1β and granulocytic inflammation as a driver of TB disease progression in humans, and suggest novel strategies for the prevention and treatment of tuberculosis.Guoliang ZhangBoping ZhouShaoyuan LiJun YueHui YangYuxin WenSenlin ZhanWenfei WangMingfeng LiaoMingxia ZhangGucheng ZengCarl G FengChristopher M SassettiXinchun ChenPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 10, Iss 10, p e1004426 (2014) |
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DOAJ |
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DOAJ |
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| topic |
Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 |
| spellingShingle |
Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Guoliang Zhang Boping Zhou Shaoyuan Li Jun Yue Hui Yang Yuxin Wen Senlin Zhan Wenfei Wang Mingfeng Liao Mingxia Zhang Gucheng Zeng Carl G Feng Christopher M Sassetti Xinchun Chen Allele-specific induction of IL-1β expression by C/EBPβ and PU.1 contributes to increased tuberculosis susceptibility. |
| description |
Mycobacterium tuberculosis infection is associated with a spectrum of clinical outcomes, from long-term latent infection to different manifestations of progressive disease. Pro-inflammatory pathways, such as those controlled by IL-1β, have the contrasting potential both to prevent disease by restricting bacterial replication, and to promote disease by inflicting tissue damage. Thus, the ultimate contribution of individual inflammatory pathways to the outcome of M. tuberculosis infection remains ambiguous. In this study, we identified a naturally-occurring polymorphism in the human IL1B promoter region, which alters the association of the C/EBPβ and PU.1 transcription factors and controls Mtb-induced IL-1β production. The high-IL-1β expressing genotype was associated with the development of active tuberculosis, the severity of pulmonary disease and poor treatment outcome in TB patients. Higher IL-1β expression did not suppress the activity of IFN-γ-producing T cells, but instead correlated with neutrophil accumulation in the lung. These observations support a specific role for IL-1β and granulocytic inflammation as a driver of TB disease progression in humans, and suggest novel strategies for the prevention and treatment of tuberculosis. |
| format |
article |
| author |
Guoliang Zhang Boping Zhou Shaoyuan Li Jun Yue Hui Yang Yuxin Wen Senlin Zhan Wenfei Wang Mingfeng Liao Mingxia Zhang Gucheng Zeng Carl G Feng Christopher M Sassetti Xinchun Chen |
| author_facet |
Guoliang Zhang Boping Zhou Shaoyuan Li Jun Yue Hui Yang Yuxin Wen Senlin Zhan Wenfei Wang Mingfeng Liao Mingxia Zhang Gucheng Zeng Carl G Feng Christopher M Sassetti Xinchun Chen |
| author_sort |
Guoliang Zhang |
| title |
Allele-specific induction of IL-1β expression by C/EBPβ and PU.1 contributes to increased tuberculosis susceptibility. |
| title_short |
Allele-specific induction of IL-1β expression by C/EBPβ and PU.1 contributes to increased tuberculosis susceptibility. |
| title_full |
Allele-specific induction of IL-1β expression by C/EBPβ and PU.1 contributes to increased tuberculosis susceptibility. |
| title_fullStr |
Allele-specific induction of IL-1β expression by C/EBPβ and PU.1 contributes to increased tuberculosis susceptibility. |
| title_full_unstemmed |
Allele-specific induction of IL-1β expression by C/EBPβ and PU.1 contributes to increased tuberculosis susceptibility. |
| title_sort |
allele-specific induction of il-1β expression by c/ebpβ and pu.1 contributes to increased tuberculosis susceptibility. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2014 |
| url |
https://doaj.org/article/c07c38f68028461ea230f61001158d03 |
| work_keys_str_mv |
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