2. Academic Validation
  3. Domain fusion TLR2-4 enhances the autophagy-dependent clearance of Staphylococcus aureus in the genetic engineering goat

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

  • Elife. 2022 Jun 28;11:e78044. doi: 10.7554/eLife.78044.
Mengyao Wang  # 1 2 3,  Yu Qi  # 1 2 3,  Yutao Cao 1 2 3,  Xiaosheng Zhang 4,  Yongsheng Wang 5,  Qingyou Liu 6,  Jinlong Zhang 4,  Guangbin Zhou 7,  Yue Ai 1 2 3,  Shao Wei 1 2 3,  Linli Wang 1 2 3,  Guoshi Liu 1 2 3,  Zhengxing Lian 1 2 3,  Hongbing Han 1 2 3
Affiliations

Affiliations

  • 1 Beijing Key Laboratory of Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing, China.
  • 2 National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, China.
  • 3 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.
  • 4 Tianjin Academy of Agricultural Sciences, Tianjin, China.
  • 5 Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest Agriculture and Forest University, Shaanxi, China.
  • 6 State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, Guangxi University, Nanning, China.
  • 7 Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China.
  • # Contributed equally.
PMID: 35762728 DOI: 10.7554/eLife.78044
Abstract

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.

Keywords

Staphylococcus aureus; Toll-like receptor 2-4; autophagy; goat; immunology; infectious disease; inflammation; macrophages; microbiology.

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