Salmonella induces flagellin- and MyD88-dependent migration of bacteria-capturing dendritic cells into the gut lumen.
OBJECTIVE
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-DeltaSalmonella pathogenicity island (SPI) 1 or Escherichia coli DH5alpha 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 (DeltafliC DeltafljB)- and SPI1-SPI2 (DeltaSPI1 DeltassrA)-deficient Salmonella, flagellated E coli K12, and MyD88 mice.


RESULTS
Salmonella DeltaSPI1 induced migration of CD11c(+)CX(3)CR1(+)MHCII(+)CD11b(-)CD8alpha(-) DCs into the small intestine, whereas flagellin- and SPI1-SPI2-deficient Salmonella, soluble flagellin, and E coli DH5alpha 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.
Arques
Juan L
JL
Programme of GI Tract Biology, Institute of Food Research, Norwich, United Kingdom.
Hautefort
Isabelle
I
Ivory
Kamal
K
Bertelli
Eugenio
E
Regoli
Marì
M
Clare
Simon
S
Hinton
Jay C D
JC
Nicoletti
Claudio
C
D000818:Animals; D039481:CD11b Antigen / Q000276:immunology / Q000378:metabolism; D039521:CD11c Antigen / Q000276:immunology / Q000378:metabolism; D002465:Cell Movement / Q000276:immunology / Q000502:physiology*; D003106:Colon / Q000166:cytology / Q000382:microbiology; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology / Q000382:microbiology; D004195:Disease Models, Animal; D005260:Female; D005408:Flagellin / Q000276:immunology / Q000378:metabolism*; D005434:Flow Cytometry; D007413:Intestinal Mucosa / Q000382:microbiology / Q000473:pathology; D007421:Intestine, Small / Q000166:cytology / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism*; D011336:Probability; D011897:Random Allocation; D012480:Salmonella Infections / Q000276:immunology / Q000503:physiopathology; D019779:Salmonella enterica / Q000276:immunology*; D012680:Sensitivity and Specificity
D039481:CD11b Antigen; D039521:CD11c Antigen; D053594:Myeloid Differentiation Factor 88; D005408:Flagellin