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

infections pose a potential threat to livestock production and public health. A novel strategy is needed to control infections due to its adaptive evolution to antibiotics. Autophagy plays a key role in degrading bacteria for innate immune cells. In order to promote clearance via Toll-like receptor (TLR)-induced autophagy pathway, the domain fusion TLR2-4 with the extracellular domain of TLR2, specific recognizing , and transmembrane and intracellular domains of TLR4 is assembled, then the goat expressing is generated. TLR2-4 substantially augments the removal of within macrophages by elevating autophagy level. Phosphorylated JNK and ERK1/2 promote LC3-puncta in TLR2-4 macrophages during -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 challenge. Moreover, the transcript of and is significantly increased via cAMP-PKA-NF-κB signaling, which facilitates -induced autophagy in TLR2-4 macrophages. Overall, the novel receptor TLR2-4 enhances the autophagy-dependent clearance of 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 infection.