Enhanced antibacterial properties of enteric glial cells attenuate intestinal inflammation through the GABABR-mediated autophagy pathway  

作　　者：Ziteng Deng Jing Lan Jiaqi Wang Lu Wang Zhihui Hao Yunfei Ma 

机构地区：[1]State Key Laboratory of Veterinary Public Health and Safety,College of Veterinary Medicine,China Agricultural University,Beijing,China

出　　处：《One Health Advances》2024年第1期151-170,共20页全健康进展(英文)

基　　金：supported by the National Natural Science Foundation of China(31772686);National Key R&D Program of China(2022YFD1801105);Beijing Municipal Natural Science Foundation(6232021).

摘　　要：Enterotoxigenic Escherichia coli(ETEC)infection is a severe threat to global public health because of its high morbidity and mortality among children and infants.Enteric glial cells(EGCs)are involved in host-bacteria com-munication.However,the mechanisms through which EGCs interact with ETEC remain unclear.We attempted to assess whetherγ-aminobutyric acid type B receptor(GABA_(B)R)activation participated in EGC autophagy dur-ing Escherichia coli K88(ETECK88)infection.Alterations in autophagy and EGC activity were observed in the intestines of the ETECK88-infected mice,and similar results were obtained from experiments in which the EGCs were directly infected with ETECK88.EGC pretreatment with specific autophagy agonists significantly decreased the inflammatory response and bacterial burden,whereas pretreatment with inhibitors had the opposite effect.Interestingly,in EGCs,GABA_(B)R activation notably increased Beclin 1 and LC3 levels and autophagosome and autolysosome numbers,thus promoting autophagy activation and enhancing antimicrobial responses against ETECK88 infection.Furthermore,GABA_(B)R defense was mediated via myeloid differentiation factor 88(MyD88)signaling in EGCs,which was proven to be based on the inhibition or overexpression of MyD88.Notably,comparable results ofGABA_(B)R activation in vivo were observed in response to ETECK88,implicating this as a defense mechanism that reinforced antibacterial activity to alleviate intestinal inflammation in mice.Our study revealed previously unappreciated roles forGABA_(B)R in link-ing EGC antibacterial autophagy to strengthen host defense against ETECK88 infection,thus identifyingGABA_(B)R as an important target for the treatment of infective enteritis.

关 键 词：Escherichia coli K88 Enteric glial cells GABA_(B)R AUTOPHAGY MYD88 

分 类 号：R73[医药卫生—肿瘤]