ResultsWe previously found that Neu3 was induced on the surface onset of colitis Using a mouse model of recurrent human food poisoning by the Salmonella enterica Typhimurium bacterial pathogen, enterocytes of the small intestine induce levels of Neu3 (green) by a TLR4-dependent mechanism. Elevated Neu3 desialylates enterocyte cell surface glycoproteins including IAP resulting in IAP endocytosis and degradation, and leading to elevated LPS-P levels in the lumen of the colon. This causes a chronic TLR4-dependent inflammatory response leading to pathology that phenocopies human Ulcerative Colitis. Enterocytes of mouse littermates shown with tubulin in red and in blue. assessed by Kaplan-Meier survival curves and log-rank tests. Data transformation methods were used if raw data does not follow normal distributions. Statistical analyses included the use of R and G*Power software.Figure 2. Acquired deficiency of IAP in the onset of colitis caused by recurrent Salmonella infectionHighest lumenal IAP enzyme concentrations exist in the small intestine, the source of IAP synthesis. IAP flow through the lumen and presence in the colon is essential to dephosphorylate LPS-phosphate produced by commensal Gram-negative bacteria. Reduce in IAP concentrations in the colon due to IAP endocytosis and degradation in the enterocytes results in reduced IAP abundance, elevated colonic LPS-phosphate, and colitis. of small intestine enterocytes in response to infection by Salmonella enterica Typhimurium (Figure 1)1). This is important as an induction of neuraminidase activity results in the reduced half-life of nascent IAP and its premature internalization and degradation. This leaves a much lower concentration of IAP throughout the lumen of the intestinal tract, with lowest levels in the distal colon (Figure 2), and resulting in elevated LPS-phosphate levels that drive TLR4-dependent inflammation Figure 1. Neu3 neuraminidase induction results the 75
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