Brooks, JohnBuckhorn, Olivia2024-07-082026-09-292024-07-082026-09-292024-04-192024-07-08http://arks.princeton.edu/ark:/88435/dsp014q77fv69vhttps://theses-dissertations.princeton.edu/handle/88435/dsp014q77fv69vGut microbial sensing is important for host gene expression and maintenance of host-microbiome associations. The loss or dysregulation of this sensing results in pathology such as inflammatory bowel disease. A key mechanism by which animals sense and respond to microorganisms is through Toll-like receptors (TLRs). These receptors are expressed on the membranes of host cells and recognize molecular components specific to bacteria and viruses. In previous work, 4-6 week-old mice were used to provide evidence that TLR signaling in intestinal epithelial cells was sufficient to induce the expression of the antimicrobial protein, Reg3g. However, in another study using 8-12 week-old mice, TLR signaling in myeloid (dendritic) cells and not in epithelial cells was shown to be sufficient for the induction of Reg3g. Given these results, I hypothesize that the cell type that senses the microbiome in the intestine changes post-weaning from epithelial to dendritic. To test this, I examined protein expression of Reg3g and the spatial separation between the small intestinal epithelium and microbiome in mice from 4 weeks of age to adulthood, across distinct genotypes. These experiments elucidate the role played by dendritic cells in sensing the microbiome and the role of the microbiome in educating the host immune system across a developmental timeline.application/pdfenPrinceton University Senior Theses