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 C57BL/6 mice were challenged with noninvasive Salmonella enterica serovar Typhimurium SL1344-ΔSalmonella pathogenicity island (SPI) 1 or Escherichia coli DH5α 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 (ΔfliC ΔfljB)- and SPI1-SPI2 (ΔSPI1 ΔssrA)-deficient Salmonella, flagellated E coli K12, and MyD88 mice.

Results

Salmonella ΔSPI1 induced migration of CD11c⁺CX₃CR1⁺MHCII⁺CD11b⁻CD8α⁻ DCs into the small intestine, whereas flagellin- and SPI1-SPI2-deficient Salmonella, soluble flagellin, and E coli DH5α 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 flagellin- and 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.

Abbreviations used in this paper: DC, dendritic cell, DiI, 1,1′-dihexadecyl-3,3,3,3-tetramethylindocarbocyanine perchlorate, GFP, green fluorescent protein, LP, lamina propria, SPI, Salmonella pathogenicity island, TEM, transmission electron microscopy, TLR, Toll-like receptor