A secreted Salmonella protein induces a proinflammatory response in epithelial cells, which promotes neutrophil migration.
In response to Salmonella typhimurium, the intestinal epithelium generates an intense inflammatory response consisting largely of polymorphonuclear leukocytes (neutrophils, PMN) migrating toward and ultimately across the epithelial monolayer into the intestinal lumen. It has been shown that bacterial-epithelial cell interactions elicit the production of inflammatory regulators that promote transepithelial PMN migration. Although S. typhimurium can enter intestinal epithelial cells, bacterial internalization is not required for the signaling mechanisms that induce PMN movement. Here, we sought to determine which S. typhimurium factors and intestinal epithelial signaling pathways elicit the production of PMN chemoattractants by enterocytes. Our results suggest that S. typhimurium activates a protein kinase C-dependent signal transduction pathway that orchestrates transepithelial PMN movement. We show that the type III effector protein, SipA, is not only necessary but is sufficient to induce this proinflammatory response in epithelial cells. Our results force us to reconsider the long-held view that Salmonella effector proteins must be directly delivered into host cells from bacterial cells.
Lee
C A
CA
Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.
Silva
M
M
Siber
A M
AM
Kelly
A J
AJ
Galyov
E
E
McCormick
B A
BA
D000199:Actins / Q000235:genetics / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology; D001426:Bacterial Proteins / Q000378:metabolism / Q000502:physiology*; D001483:Base Sequence; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D017931:DNA Primers; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000473:pathology; D018836:Inflammation Mediators / Q000502:physiology*; D007413:Intestinal Mucosa / Q000473:pathology*; D008840:Microfilament Proteins; D009504:Neutrophils / Q000166:cytology* / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D012486:Salmonella typhimurium / Q000235:genetics / Q000378:metabolism*
D000199:Actins; D000911:Antibodies, Monoclonal; D001426:Bacterial Proteins; D017931:DNA Primers; D004791:Enzyme Inhibitors; D018836:Inflammation Mediators; D008840:Microfilament Proteins; C118287:SipA protein, Salmonella; D011493:Protein Kinase C