Molecular Mechanism Of Leucine In The Regulation Of Swine Intestinal Antiviral Innate Immunity

As a functional amino acid,leucine has numerous physiological functions.This study intends to explore the role of leucine in regulating cellular antiviral innate immunity and its molecular mechanism through in vitro cell experiments.In this study,intestinal porcine epithelial cells(IPEC-J2)were used as experimental subjects to study the molecular mechanism of leucine regulation of innate immunity.We found that leucine can induce the expression of PRRs genes such as IFN-? and RIG-I in porcine intestinal epithelial cells and positively regulate host antiviral responses.To investigate whether Sestrin2-mTORC1 and IRF3 are involved in leucine-mediated antiviral innate immunity,we knocked down the expression of IRF3,Sestrin2,and mTORC1 by shRNA interference technology.We found that leucine activates the IRF3 pathway and regulates the expression of IFN-? and PRRs genes positively.At the same time,Sestrin2 is involved in leucine-induced activation of mTORC1 in intestinal epithelial cells,inhibits anti-viral response in host intestinal epithelial cells,and inhibits leucine Induction of expression of innate immune-related genes.This suggests that mTORC1 may be involved in leucine regulation of the antiviral innate immune response.After knocking down mTORC1,we found that the expression levels of IFN-?,RIG-I,MDA-5 and TLR-3 were decreased.At the same time,the addition of the rapamycin treatment group revealed that the activation of IRF3 was also inhibited.These results indicate that mTORC1 is critical for leucine-induced IRF3 activation.In summary,in porcine intestinal epithelial cells,leucine can regulate the activation of the transcription factor IRF3 via the signaling pathway of Sestrin2-mTORC1 and activate antiviral innate immunity.