A secreted <i>Salmonella</i> protein induces a proinflammatory response in epithelial cells, which promotes neutrophil migration

<jats:p> In response to <jats:italic>Salmonella typhimurium</jats:italic> , 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 <jats:italic>S. typhimurium</jats:italic> can enter intestinal epithelial cells, bacterial internalization is not required for the signaling mechanisms that induce PMN movement. Here, we sought to determine which <jats:italic>S. typhimurium</jats:italic> factors and intestinal epithelial signaling pathways elicit the production of PMN chemoattractants by enterocytes. Our results suggest that <jats:italic>S. typhimurium</jats:italic> 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 <jats:italic>Salmonella</jats:italic> effector proteins must be directly delivered into host cells from bacterial cells. </jats:p>