Project description:Using DropSeq single cell RNA sequencing, we report that neuronal derived-IL-18 is required for goblet cell expression of intestinal antimicrobial protein expression Mucosal barrier immunity is essential for the maintenance of the commensal microflora and combating invasive bacterial infection. Although immune and epithelial cells are thought to be the canonical orchestrators of this complex equilibrium, here we show that the enteric nervous system (ENS) plays an essential and non-redundant role in governing the anti-microbial protein (AMP) response. Using confocal microscopy and single-molecule fluorescence in situ mRNA-hybridization (smFISH) studies, we observed that intestinal neurons produce the pleiotropic cytokine IL-18. Strikingly, deletion of IL-18 from the enteric neurons alone, but not immune or epithelial cells, rendered mice susceptible to invasive Salmonella typhimurium (S.t.) infection. Mechanistically, unbiased RNA sequencing and single cell sequencing revealed that enteric neuronal IL-18 is specifically required for homeostatic goblet cell AMP production. Together, we show that neuron derived IL-18 signaling controls tissue wide intestinal immunity and has profound consequences on the mucosal barrier and invasive bacterial killing.
Project description:Using RNA sequencing, we report that neuron derived-IL-18 is required for intestinal antimicrobial protein expression Mucosal barrier immunity is essential for the maintenance of the commensal microflora and combating invasive bacterial infection. Although immune and epithelial cells are thought to be the canonical orchestrators of this complex equilibrium, here we show that the enteric nervous system (ENS) plays an essential and non-redundant role in governing the anti-microbial protein (AMP) response. Using confocal microscopy and single-molecule fluorescence in situ mRNA-hybridization (smFISH) studies, we observed that intestinal neurons produce the pleiotropic cytokine IL-18. Strikingly, deletion of IL-18 from the enteric neurons alone, but not immune or epithelial cells, rendered mice susceptible to invasive Salmonella typhimurium (S.t.) infection. Mechanistically, unbiased RNA sequencing and single cell sequencing revealed that enteric neuronal IL-18 is specifically required for homeostatic goblet cell AMP production. Together, we show that neuron derived IL-18 signaling controls tissue wide intestinal immunity and has profound consequences on the mucosal barrier and invasive bacterial killing.
Project description:The enteric nervous system (ENS) can control most essential gut functions owing to its organization into complete neural circuits consisting of a multitude of different neuronal subtypes. We used microarrays to identify transcription factor networks and signaling pathways involved in diversification and differentiation of enteric neurons during development of the enteric nervous system.
Project description:Enteric nervous system is involved in the regulation of intestinal inflammation. We developped mouse primary cultures of enteric nervous system to study impact of LPS, as pro-inflammatory mediator, and of the pro-drug 6-mercaptopurine on enteric inflammatory pathways We used microarrays to detail the global programme of gene expression underlying enteric neuro-inflammation and identified classes of up-regulated genes during this process.
Project description:To identify the gene expression profile of enteric glia and assess the transcriptional similarity between enteric and extraenteric glia, we performed RNA sequencing analysis on PLP1-expressing cells in the mouse intestine. This analysis shows that enteric glia are transcriptionally unique and distinct from other cell types in the nervous system. Enteric glia express many genes characteristic of the myelinating glia, Schwann cells and oli- godendrocytes, although there is no evidence of myelination in the murine ENS. Total RNA expression profiles of PLP1 expressing enteric glial cells (GFP+) and non-glial cells (GFP-negative) were obtained from the ileum and colon of juvenile PLP1-eGFP transgenic mice.