Figure 7

Working model for the pathogenesis of colonic ion transport in fatal diarrhea in C. rodentium-infected FVB mice. Normal ion transport in the large intestine is mediated largely by the coupled action of the anion exchanger DRA, CFTR, sodium/proton exchangers NHE2/3, potassium transporters and carbonic anhydrases (see Discussion). (a) alterations in ion transport in C. rodentium-infected SW mice, including subtle decreases in expression of some apical transporters and compensatory increases in basolateral water channel Aqp4 expression. (b) Profound changes in infected FVB mice consisting of mild to marked downregulation of the majority of apical transporters involved in intestinal Na⁺ and Cl^- absorption and bicarbonate secretion, along with upregulation of basolateral transporters providing the driving force for chloride secretion. In addition, constitutively higher levels of Pept2 and Adora2b expression in FVB mice (indicated by asterisks) can contribute to alterations in cytosolic pH and cAMP during infection, thereby further affecting ion exchange. The cumulative effect may ultimately result in severe diarrhea and lead to death in these susceptible animals. Vesicular trafficking of some proteins (A2B receptor, aquaporins, NHE3, ATPases) and paracellular transport are not addressed here. Colors indicate fold change in gene expression identified by microarray or qRT-PCR: light green ≥2-fold decrease; dark green ≥8-fold decrease; pink ≥2-fold increase; red ≥8-fold increase.