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Domain fusion TLR2-4 enhances the autophagy-dependent clearance of Staphylococcus aureus in the genetic engineering goat

Staphylococcus aureus infections pose a potential threat to livestock production and public health. A novel strategy is needed to control S. aureus infections due to its adaptive evolution to antibiotics. Autophagy plays a key role in degrading bacteria for innate immune cells. In order to promote S...

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Autores principales: Wang, Mengyao, Qi, Yu, Cao, Yutao, Zhang, Xiaosheng, Wang, Yongsheng, Liu, Qingyou, Zhang, Jinlong, Zhou, Guangbin, Ai, Yue, Wei, Shao, Wang, Linli, Liu, Guoshi, Lian, Zhengxing, Han, Hongbing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9239677/
https://www.ncbi.nlm.nih.gov/pubmed/35762728
http://dx.doi.org/10.7554/eLife.78044
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author Wang, Mengyao
Qi, Yu
Cao, Yutao
Zhang, Xiaosheng
Wang, Yongsheng
Liu, Qingyou
Zhang, Jinlong
Zhou, Guangbin
Ai, Yue
Wei, Shao
Wang, Linli
Liu, Guoshi
Lian, Zhengxing
Han, Hongbing
author_facet Wang, Mengyao
Qi, Yu
Cao, Yutao
Zhang, Xiaosheng
Wang, Yongsheng
Liu, Qingyou
Zhang, Jinlong
Zhou, Guangbin
Ai, Yue
Wei, Shao
Wang, Linli
Liu, Guoshi
Lian, Zhengxing
Han, Hongbing
author_sort Wang, Mengyao
collection PubMed
description Staphylococcus aureus infections pose a potential threat to livestock production and public health. A novel strategy is needed to control S. aureus infections due to its adaptive evolution to antibiotics. Autophagy plays a key role in degrading bacteria for innate immune cells. In order to promote S. aureus clearance via Toll-like receptor (TLR)-induced autophagy pathway, the domain fusion TLR2-4 with the extracellular domain of TLR2, specific recognizing S. aureus, and transmembrane and intracellular domains of TLR4 is assembled, then the goat expressing TLR2-4 is generated. TLR2-4 substantially augments the removal of S. aureus within macrophages by elevating autophagy level. Phosphorylated JNK and ERK1/2 promote LC3-puncta in TLR2-4 macrophages during S. aureus-induced autophagy via MyD88 mediated the TAK1 signaling cascade. Meantime, the TRIF-dependent TBK1-TFEB-OPTN signaling is involved in TLR2-4-triggered autophagy after S. aureus challenge. Moreover, the transcript of ATG5 and ATG12 is significantly increased via cAMP-PKA-NF-κB signaling, which facilitates S. aureus-induced autophagy in TLR2-4 macrophages. Overall, the novel receptor TLR2-4 enhances the autophagy-dependent clearance of S. aureus in macrophages via TAK1/TBK1-JNK/ERK, TBK1-TFEB-OPTN, and cAMP-PKA-NF-κB-ATGs signaling pathways, which provide an alternative approach for resistant against S. aureus infection.
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spelling pubmed-92396772022-06-29 Domain fusion TLR2-4 enhances the autophagy-dependent clearance of Staphylococcus aureus in the genetic engineering goat Wang, Mengyao Qi, Yu Cao, Yutao Zhang, Xiaosheng Wang, Yongsheng Liu, Qingyou Zhang, Jinlong Zhou, Guangbin Ai, Yue Wei, Shao Wang, Linli Liu, Guoshi Lian, Zhengxing Han, Hongbing eLife Immunology and Inflammation Staphylococcus aureus infections pose a potential threat to livestock production and public health. A novel strategy is needed to control S. aureus infections due to its adaptive evolution to antibiotics. Autophagy plays a key role in degrading bacteria for innate immune cells. In order to promote S. aureus clearance via Toll-like receptor (TLR)-induced autophagy pathway, the domain fusion TLR2-4 with the extracellular domain of TLR2, specific recognizing S. aureus, and transmembrane and intracellular domains of TLR4 is assembled, then the goat expressing TLR2-4 is generated. TLR2-4 substantially augments the removal of S. aureus within macrophages by elevating autophagy level. Phosphorylated JNK and ERK1/2 promote LC3-puncta in TLR2-4 macrophages during S. aureus-induced autophagy via MyD88 mediated the TAK1 signaling cascade. Meantime, the TRIF-dependent TBK1-TFEB-OPTN signaling is involved in TLR2-4-triggered autophagy after S. aureus challenge. Moreover, the transcript of ATG5 and ATG12 is significantly increased via cAMP-PKA-NF-κB signaling, which facilitates S. aureus-induced autophagy in TLR2-4 macrophages. Overall, the novel receptor TLR2-4 enhances the autophagy-dependent clearance of S. aureus in macrophages via TAK1/TBK1-JNK/ERK, TBK1-TFEB-OPTN, and cAMP-PKA-NF-κB-ATGs signaling pathways, which provide an alternative approach for resistant against S. aureus infection. eLife Sciences Publications, Ltd 2022-06-28 /pmc/articles/PMC9239677/ /pubmed/35762728 http://dx.doi.org/10.7554/eLife.78044 Text en © 2022, Wang, Qi et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Immunology and Inflammation
Wang, Mengyao
Qi, Yu
Cao, Yutao
Zhang, Xiaosheng
Wang, Yongsheng
Liu, Qingyou
Zhang, Jinlong
Zhou, Guangbin
Ai, Yue
Wei, Shao
Wang, Linli
Liu, Guoshi
Lian, Zhengxing
Han, Hongbing
Domain fusion TLR2-4 enhances the autophagy-dependent clearance of Staphylococcus aureus in the genetic engineering goat
title Domain fusion TLR2-4 enhances the autophagy-dependent clearance of Staphylococcus aureus in the genetic engineering goat
title_full Domain fusion TLR2-4 enhances the autophagy-dependent clearance of Staphylococcus aureus in the genetic engineering goat
title_fullStr Domain fusion TLR2-4 enhances the autophagy-dependent clearance of Staphylococcus aureus in the genetic engineering goat
title_full_unstemmed Domain fusion TLR2-4 enhances the autophagy-dependent clearance of Staphylococcus aureus in the genetic engineering goat
title_short Domain fusion TLR2-4 enhances the autophagy-dependent clearance of Staphylococcus aureus in the genetic engineering goat
title_sort domain fusion tlr2-4 enhances the autophagy-dependent clearance of staphylococcus aureus in the genetic engineering goat
topic Immunology and Inflammation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9239677/
https://www.ncbi.nlm.nih.gov/pubmed/35762728
http://dx.doi.org/10.7554/eLife.78044
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