The extracellular murine pathogen Citrobacter rodentium is commonly used to model human infections by the diarrhoeal pathogens enteropathogenic Escherichia coli and enterohaemorrhagic E. coli. These pathogens adhere intimately to intestinal epithelial cells during infection and inject virulence proteins via a Type 3 Secretion System. Upon enteric infection, an interplay of complex pathogen-host interactions ensues at the mucosa, mediated by proteins of both host origin, including antimicrobial peptides and cytokines, in addition to those of pathogen origin, namely virulence proteins. In this work I explored the responses of colonic intestinal epithelial cells and caecal patch tissue to C. rodentium infection in a temporal manner utilising advanced isobaric labelling proteomics combined with more traditional validation techniques, including quantitative PCR, immunohistochemistry and cytokine quantification. Through this platform, this thesis reveals induction of key host responses early during infection, including a switch to aerobic glycolysis and perturbation of cholesterol homeostasis. IL-22 is also implicated in this metabolic switch, moreover, is found to be involved in the characteristic depletion of goblet cells that occurs during infection. Finally, events occurring in the caecal patch during C. rodentium infection are documented for the first time at a high level of temporal resolution, revealing a dramatic shift to adaptive responses occurring by 13 DPI. The findings presented herein contribute to the ever-increasing understanding of host responses to infection and underscore the importance of studying different time-points during the progression of disease.