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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...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2022
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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. |
format | Online Article Text |
id | pubmed-9239677 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
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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