PMID- 35531887 OWN - NLM STAT- MEDLINE DCOM- 20220524 LR - 20220716 IS - 2150-5608 (Electronic) IS - 2150-5594 (Print) IS - 2150-5594 (Linking) VI - 13 IP - 1 DP - 2022 Dec TI - Guanylate-Binding protein 2b regulates the AMPK/mTOR/ULK1 signalling pathway to induce autophagy during Mycobacterium bovis infection. PG - 875-889 LID - 10.1080/21505594.2022.2073024 [doi] AB - Autophagic isolation and degradation of intracellular pathogens are employed by host cells as primary innate immune defense mechanisms to control intercellular M. bovis infection. In this study, RNA-Seq technology was used to obtain the total mRNA from bone marrow-derived macrophages (BMDMs) infected with M. bovis at 6 and 24 h after infection. One of the differential genes, GBP2b, was also investigated. Analysis of the significant pathway involved in GBP2b-coexpressed mRNA demonstrated that GBP2b was associated with autophagy and autophagy-related mammalian target of rapamycin (mTOR) signaling and AMP-activated protein kinase (AMPK) signaling. The results of in vivo and in vitro experiments showed significant up-regulation of GBP2b during M. bovis infection. For in vitro validation, small interfering RNA-GBP2b plasmids were transfected into BMDMs and RAW264.7 cells lines to down-regulate the expression of GBP2b. The results showed that the down-regulation of GBP2b impaired autophagy via the AMPK/mTOR/ULK1 pathway, thereby promoting the intracellular survival of M. bovis. Further studies revealed that the activation of AMPK signaling was essential for the regulation of autophagy during M. bovis infection. These findings expand the understanding of how GBP2b regulates autophagy and suggest that GBP2b may be a potential target for the treatment of diseases caused by M. bovis. FAU - Yu, Youli AU - Yu Y AD - MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China. FAU - Pan, Jialiang AU - Pan J AD - MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China. FAU - Liu, Mengting AU - Liu M AD - MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China. FAU - Jiang, Haiqin AU - Jiang H AUID- ORCID: 0000-0002-4924-0465 AD - Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China. FAU - Xiong, Jingshu AU - Xiong J AD - Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China. FAU - Tao, Lei AU - Tao L AD - Nanjing Institute for Food and Drug Control, Nanjing, China. FAU - Xue, Feng AU - Xue F AD - MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China. FAU - Tang, Fang AU - Tang F AD - MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China. FAU - Wang, Hongsheng AU - Wang H AD - Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China. FAU - Dai, Jianjun AU - Dai J AD - China Pharmaceutical University, Nanjing, China. LA - eng SI - figshare/10.6084/m9.figshare.16696033v3 PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Virulence JT - Virulence JID - 101531386 RN - 0 (Carrier Proteins) RN - 0 (RNA, Messenger) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - EC 2.7.11.31 (AMP-Activated Protein Kinases) SB - IM MH - AMP-Activated Protein Kinases/genetics/metabolism MH - Autophagy/genetics MH - Carrier Proteins MH - *Mycobacterium bovis/genetics MH - RNA, Messenger MH - TOR Serine-Threonine Kinases/genetics/metabolism PMC - PMC9132469 OTO - NOTNLM OT - AMPK OT - GBP2b OT - Mycobacterium bovis OT - RNA-Seq OT - ULK1 OT - autophagy OT - mTOR COIS- No potential conflict of interest was reported by the author(s). EDAT- 2022/05/10 06:00 MHDA- 2022/05/25 06:00 PMCR- 2022/05/21 CRDT- 2022/05/09 05:31 PHST- 2022/05/10 06:00 [pubmed] PHST- 2022/05/25 06:00 [medline] PHST- 2022/05/09 05:31 [entrez] PHST- 2022/05/21 00:00 [pmc-release] AID - 2073024 [pii] AID - 10.1080/21505594.2022.2073024 [doi] PST - ppublish SO - Virulence. 2022 Dec;13(1):875-889. doi: 10.1080/21505594.2022.2073024.