Salmonella Induces Flagellin- and MyD88-Dependent Migration of Bacteria-Capturing Dendritic Cells Into the Gut Lumen

BACKGROUND & AIMS: Intestinal dendritic cells (DCs) sample bacteria, such as Salmonella, by extending cellular processes into the lumen to capture bacteria and shuttle them across the epithelium; however, direct evidence of bacteria-loaded DCs travelling back into the tissue is lacking. We hypothesized that sampling is paralleled by migration of DCs into the lumen prior to or following the internalization of Salmonella. METHODS: The small intestine and the colon of BALB/c and CS7BL/6 mice were challenged with noninvasive Salmonella enterica serovar Typhimurium SL1344-Delta Salmonella pathogenicity island (SPI) 1 or Escherichia coli DHS alpha by using isolated loops or oral administration by gavage. Transepithelial migration of DCs was documented by immunohistochemistry, microscopy, and flow cytometry. The role of flagellin was determined by using flagellin (Delta fliC Delta fljB)- and SPI1-SPI2 (Delta SPI1 Delta ssrA)-deficient Salmonella, flagellated E coli K12, and MyD88 mice. RESULTS: Salmonella Delta SPI1 induced migration of CD11c(+)CX(3)CR1(+)MHCII(+)CD11b(-)CD8 alpha(-) DCs into the small intestine, whereas flagellin- and SPI1-SP12-deficient Salmonella, soluble flagellin, and E coli DHSa or flagellated K12, failed to do so. DC migration did not occur in the colon; it was not observed in MyD88 mice, and intraluminal DCs internalized Salmonella but did not cross the epithelium to return into tissues. Finally, DC migration was not linked to Salmonella-induced damage of the epithelium. CONCLUSIONS: DC-mediated sampling of Salmonella is accompanied by flagellinand MyD88-dependent migration of Salmonella-capturing DCs into the intestinal lumen. We suggest that the rapid intraluminal migration of Salmonella-capturing DCs may play a role in the protection of the intestinal mucosa against bacterial infection.