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

Mengyao Wang; Yu Qi; Yutao Cao; Xiaosheng Zhang; Yongsheng Wang; Qingyou Liu; Jinlong Zhang; Guangbin Zhou; Yue Ai; Shao Wei; Linli Wang; Guoshi Liu; Zhengxing Lian; Hongbing Han

doi:10.7554/eLife.78044

eLife (Jun 2022)

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

Mengyao Wang,
Yu Qi,
Yutao Cao,
Xiaosheng Zhang,
Yongsheng Wang,
Qingyou Liu,
Jinlong Zhang,
Guangbin Zhou,
Yue Ai,
Shao Wei,
Linli Wang,
Guoshi Liu,
Zhengxing Lian,
Hongbing Han

Affiliations

Mengyao Wang: ORCiD; Beijing Key Laboratory of Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing, China; National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, China; Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, China Agricultural University, Beijing, China
Yu Qi: Beijing Key Laboratory of Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing, China; National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, China; Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, China Agricultural University, Beijing, China
Yutao Cao: Beijing Key Laboratory of Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing, China; National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, China; Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, China Agricultural University, Beijing, China
Xiaosheng Zhang: Tianjin Academy of Agricultural Sciences, Tianjin, China
Yongsheng Wang: Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest Agriculture and Forest University, Shaanxi, China
Qingyou Liu: State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, Guangxi University, Nanning, China
Jinlong Zhang: Tianjin Academy of Agricultural Sciences, Tianjin, China
Guangbin Zhou: ORCiD; Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China
Yue Ai: Beijing Key Laboratory of Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing, China; National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, China; Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, China Agricultural University, Beijing, China
Shao Wei: Beijing Key Laboratory of Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing, China; National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, China; Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, China Agricultural University, Beijing, China
Linli Wang: Beijing Key Laboratory of Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing, China; National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, China; Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, China Agricultural University, Beijing, China
Guoshi Liu: Beijing Key Laboratory of Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing, China; National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, China; Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, China Agricultural University, Beijing, China
Zhengxing Lian: Beijing Key Laboratory of Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing, China; National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, China; Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, China Agricultural University, Beijing, China
Hongbing Han: ORCiD; Beijing Key Laboratory of Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing, China; National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, China; Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, China Agricultural University, Beijing, China

DOI: https://doi.org/10.7554/eLife.78044
Journal volume & issue: Vol. 11

Abstract

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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.

Published in eLife

ISSN: 2050-084X (Online)
Publisher: eLife Sciences Publications Ltd
Country of publisher: United Kingdom
LCC subjects: Medicine; Science: Biology (General)
Website: https://elifesciences.org

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