MiRNA-AIEC · Role of microRNAs in host responses to Crohn's disease-associated adherent-invasive Escherichia coli

Recent studies have shown dysregulation of microRNAs (miRNAs) in the mucosa of Crohn’s disease (CD) patients, suggesting a role for miRNAs as contributors to inflammatory bowel disease (IBD) susceptibility. The scientists from the host institution previously showed that ileal lesions in CD patients are colonized by pathogenic adherent-invasive Escherichia coli (AIEC), which are able to invade and to replicate within intestinal epithelial cells, and that functional autophagy is required to restrain AIEC replication. The overall hypothesis of this proposal is that miRNA pathway contributes to innate immune responses to AIEC colonization and/or inflammatory activities. The goal of our study is to determine the microRNAs dysregulated in host cells upon infection with AIEC, and the mechanism through which they contribute to responses of the host. In particular, three objectives will be addressed in this project: 1) To determine the potential role and mechanism by which miRNAs modulate the host responses of intestinal epithelial cells (IECs) to AIEC; 2) To investigate the regulation of CEACAM6, a host receptor for AIEC, by miRNAs in IECs during pathophysiological state, and in host responses to AIEC infection; and 3) To test the hypothesis that AIEC impair autophagy to replicate in host cells by modulating expression of host miRNAs. I propose to use IEC culture models of AIEC infection accompanied with bioinformatics tools to identify the miRNAs which are regulators of the key signaling pathways that modulate cross-talk between AIEC and host cells. The proposed studies in this project will shed light on the mechanism by which miRNAs are involved in host responses to AIEC infection, which could help to identify new biomarkers and potential therapeutic targets for IBD.