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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Autores principales: Zhongfan Zheng, Yilixiati Aihemaiti, Junqiang Liu, Muhammad Irfan Afridi, Shengmei Yang, Xiumei Zhang, Yongfu Xu, Chunhong Chen, Haijun Tu
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Publicado: Frontiers Media S.A. 2021
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Acceso en línea:https://doaj.org/article/c4723467dfc648619ffc711b828a59c5
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spelling 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)
institution DOAJ
collection DOAJ
language EN
topic 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
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