Flagellin stimulation of intestinal epithelial cells triggers CCL20-mediated migration of dendritic cells.
Enteropathogenic bacteria elicit mucosal innate and adaptive immune responses. We investigated whether gut epithelial cells played a role in triggering an adaptive immune response by recruiting dendritic cells (DCs). Immature DCs are selectively attracted by the CCL20 chemokine. The expression of the CCL20 gene in human intestinal epithelial cell lines was up-regulated by pathogenic bacteria, including Salmonella species, but not by indigenous bacteria of the intestinal flora. The Salmonella machinery for epithelial cell invasion was not required for CCL20 gene activation. Flagellin but not the lipopolysaccharide was found to be the Salmonella factor responsible for stimulation of epithelial CCL20 production. CCL20 in turn triggered a specific migration of immature DCs. Our data show that crosstalk between bacterial flagellin and epithelial cells is essential for the recruitment of DCs, a mechanism that could be instrumental to initiate adaptive immune responses in the gut.
Sierro
F
F
Swiss Institute for Experimental Cancer Research, Chemin des Boveresses 155, 1066 Epalinges, Switzerland.
Dubois
B
B
Coste
A
A
Kaiserlian
D
D
Kraehenbuhl
J P
JP
Sirard
J C
JC
D001419:Bacteria / Q000276:immunology; D018938:Caco-2 Cells; D002460:Cell Line; D054418:Chemokine CCL20; D019742:Chemokines, CC / Q000235:genetics / Q000276:immunology*; D002633:Chemotaxis / Q000502:physiology*; D003470:Culture Media; D003713:Dendritic Cells / Q000276:immunology*; D004847:Epithelial Cells / Q000276:immunology / Q000382:microbiology; D005408:Flagellin / Q000276:immunology*; D015870:Gene Expression; D006361:Heating; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology*; D019402:Macrophage Inflammatory Proteins / Q000235:genetics / Q000276:immunology*; D054399:Receptors, CCR6; D019707:Receptors, Chemokine; D012486:Salmonella typhimurium / Q000276:immunology
C108355:CCL20 protein, human; C106311:CCR6 protein, human; D054418:Chemokine CCL20; D019742:Chemokines, CC; D003470:Culture Media; D019402:Macrophage Inflammatory Proteins; D054399:Receptors, CCR6; D019707:Receptors, Chemokine; D005408:Flagellin