The bZIP Transcription Factor ZIP-11 Is Required for the Innate Immune Regulation in Caenorhabditis elegans
Innate immunity is the first line of host defense against pathogen infection in metazoans. However, the molecular mechanisms of the complex immune regulatory network are not fully understood. Based on a transcriptome profiling of the nematode Caenorhabditis elegans, we found that a bZIP transcriptio...
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Frontiers Media S.A.
2021
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oai:doaj.org-article:c4723467dfc648619ffc711b828a59c52021-11-05T11:33:13ZThe bZIP Transcription Factor ZIP-11 Is Required for the Innate Immune Regulation in Caenorhabditis elegans1664-322410.3389/fimmu.2021.744454https://doaj.org/article/c4723467dfc648619ffc711b828a59c52021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.744454/fullhttps://doaj.org/toc/1664-3224Innate immunity is the first line of host defense against pathogen infection in metazoans. However, the molecular mechanisms of the complex immune regulatory network are not fully understood. Based on a transcriptome profiling of the nematode Caenorhabditis elegans, we found that a bZIP transcription factor ZIP-11 was up-regulated upon Pseudomonas aeruginosa PA14 infection. The tissue specific RNAi knock-down and rescue data revealed that ZIP-11 acts in intestine to promote host resistance against P. aeruginosa PA14 infection. We further showed that intestinal ZIP-11 regulates innate immune response through constituting a feedback loop with the conserved PMK-1/p38 mitogen-activated protein signaling pathway. Intriguingly, ZIP-11 interacts with a CCAAT/enhancer-binding protein, CEBP-2, to mediate the transcriptional response to P. aeruginosa PA14 infection independently of PMK-1/p38 pathway. In addition, human homolog ATF4 can functionally substitute for ZIP-11 in innate immune regulation of C. elegans. Our findings indicate that the ZIP-11/ATF4 genetic program activates local innate immune response through conserved PMK-1/p38 and CEBP-2/C/EBPγ immune signals in C. elegans, raising the possibility that a similar process may occur in other organisms.Zhongfan ZhengZhongfan ZhengYilixiati AihemaitiYilixiati AihemaitiJunqiang LiuJunqiang LiuMuhammad Irfan AfridiMuhammad Irfan AfridiShengmei YangShengmei YangXiumei ZhangXiumei ZhangYongfu XuYongfu XuChunhong ChenChunhong ChenHaijun TuHaijun TuFrontiers Media S.A.articleinnate immunitybZIP transcription factorintestineATF4/ZIP-11PMK-1/p38CEBP-2Immunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021) |
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innate immunity bZIP transcription factor intestine ATF4/ZIP-11 PMK-1/p38 CEBP-2 Immunologic diseases. Allergy RC581-607 |
spellingShingle |
innate immunity bZIP transcription factor intestine ATF4/ZIP-11 PMK-1/p38 CEBP-2 Immunologic diseases. Allergy RC581-607 Zhongfan Zheng Zhongfan Zheng Yilixiati Aihemaiti Yilixiati Aihemaiti Junqiang Liu Junqiang Liu Muhammad Irfan Afridi Muhammad Irfan Afridi Shengmei Yang Shengmei Yang Xiumei Zhang Xiumei Zhang Yongfu Xu Yongfu Xu Chunhong Chen Chunhong Chen Haijun Tu Haijun Tu The bZIP Transcription Factor ZIP-11 Is Required for the Innate Immune Regulation in Caenorhabditis elegans |
description |
Innate immunity is the first line of host defense against pathogen infection in metazoans. However, the molecular mechanisms of the complex immune regulatory network are not fully understood. Based on a transcriptome profiling of the nematode Caenorhabditis elegans, we found that a bZIP transcription factor ZIP-11 was up-regulated upon Pseudomonas aeruginosa PA14 infection. The tissue specific RNAi knock-down and rescue data revealed that ZIP-11 acts in intestine to promote host resistance against P. aeruginosa PA14 infection. We further showed that intestinal ZIP-11 regulates innate immune response through constituting a feedback loop with the conserved PMK-1/p38 mitogen-activated protein signaling pathway. Intriguingly, ZIP-11 interacts with a CCAAT/enhancer-binding protein, CEBP-2, to mediate the transcriptional response to P. aeruginosa PA14 infection independently of PMK-1/p38 pathway. In addition, human homolog ATF4 can functionally substitute for ZIP-11 in innate immune regulation of C. elegans. Our findings indicate that the ZIP-11/ATF4 genetic program activates local innate immune response through conserved PMK-1/p38 and CEBP-2/C/EBPγ immune signals in C. elegans, raising the possibility that a similar process may occur in other organisms. |
format |
article |
author |
Zhongfan Zheng Zhongfan Zheng Yilixiati Aihemaiti Yilixiati Aihemaiti Junqiang Liu Junqiang Liu Muhammad Irfan Afridi Muhammad Irfan Afridi Shengmei Yang Shengmei Yang Xiumei Zhang Xiumei Zhang Yongfu Xu Yongfu Xu Chunhong Chen Chunhong Chen Haijun Tu Haijun Tu |
author_facet |
Zhongfan Zheng Zhongfan Zheng Yilixiati Aihemaiti Yilixiati Aihemaiti Junqiang Liu Junqiang Liu Muhammad Irfan Afridi Muhammad Irfan Afridi Shengmei Yang Shengmei Yang Xiumei Zhang Xiumei Zhang Yongfu Xu Yongfu Xu Chunhong Chen Chunhong Chen Haijun Tu Haijun Tu |
author_sort |
Zhongfan Zheng |
title |
The bZIP Transcription Factor ZIP-11 Is Required for the Innate Immune Regulation in Caenorhabditis elegans |
title_short |
The bZIP Transcription Factor ZIP-11 Is Required for the Innate Immune Regulation in Caenorhabditis elegans |
title_full |
The bZIP Transcription Factor ZIP-11 Is Required for the Innate Immune Regulation in Caenorhabditis elegans |
title_fullStr |
The bZIP Transcription Factor ZIP-11 Is Required for the Innate Immune Regulation in Caenorhabditis elegans |
title_full_unstemmed |
The bZIP Transcription Factor ZIP-11 Is Required for the Innate Immune Regulation in Caenorhabditis elegans |
title_sort |
bzip transcription factor zip-11 is required for the innate immune regulation in caenorhabditis elegans |
publisher |
Frontiers Media S.A. |
publishDate |
2021 |
url |
https://doaj.org/article/c4723467dfc648619ffc711b828a59c5 |
work_keys_str_mv |
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