A secretedSalmonellaprotein induces a proinflammatory response in epithelial cells, which promotes neutrophil migration

• DOI: 10.1073/pnas.97.22.12283
• Publication Date: 2002-07-26T14:36:44Z
• Authors: Catherine A. Lee; Milton Silva; Andrew M. Siber; Aaron J. Kelly; Edouard Galyov; Beth A. McCormick
• Keywords: Salmonella typhimurium; 0301 basic medicine; Cultured; Base Sequence; Neutrophils; Cells; Microfilament Proteins; 610; Antibodies, Monoclonal; Epithelial Cells; Antibodies; Actins; 3. Good health; 03 medical and health sciences; Bacterial Proteins; Cell Movement; Monoclonal; Enzyme Inhibitors; Inflammation Mediators; Intestinal Mucosa; Cells, Cultured; Protein Kinase C; DNA Primers

In response toSalmonella 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. AlthoughS. typhimuriumcan enter intestinal epithelial cells, bacterial internalization is not required for the signaling mechanisms that induce PMN movement. Here, we sought to determine whichS. typhimuriumfactors and intestinal epithelial signaling pathways elicit the production of PMN chemoattractants by enterocytes. Our results suggest thatS. typhimuriumactivates 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 thatSalmonellaeffector proteins must be directly delivered into host cells from bacterial cells.