Colonic Goblet Cell Activity and Proinflammatory Responses Are Spatially Regulated in the Colon in Citrobacter...

Diarrheal disease causes 1.5 million deaths each year. Among the causative agents, enteropathogenic and enterohemorrhagic Escherichia coli are of particular concern. Citrobacter rodentium is a murine pathobiont used to model enteropathogenic E. coli and enterohemorrhagic E. coli infections because of shared virulence mechanisms and disease features, with infection exhibiting a distinct spatial distribution within the colon, by an unknown mechanism. The hypothesis of this study was that regional innate immune responses mediated by colonic goblet cells and proinflammatory cytokines contribute to the spatial distribution of C. rodentium in the colon. To interrogate this, mucus production, proinflammatory responses, and goblet cell lineage activity were assessed as potential drivers of C. rodentium site selection in the colon. C57BL/6 mice were infected with either DBS100 or fluorescent C. rodentium, and bacterial burden, localization, intestinal permeability, and cytokine expression were analyzed. Whole-body imaging showed high bacterial infection in the mid and distal colon, with corresponding elevated expression of proinflammatory cytokines in these regions. In contrast, analysis of key mucus proteins revealed region-specific differences, with goblet cell lineage markers and Muc2 expression significantly up-regulated only in the proximal colon, associated with enhanced protection against bacterial colonization in this region. These findings demonstrate that goblet cells and proinflammatory cytokines influence the regional distribution of C. rodentium infection and that mucus-associated protein regulation occurred independently of MUC2.