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 le ukocytes (neutrophils, PMN) migrating toward and ultimately across the epit helial monolayer into the intestinal lumen. It has been shown that bacteria l-epithelial cell interactions elicit the production of inflammatory regula tors that promote transepithelial PMN migration. Although S. typhimurium ca n enter intestinal epithelial cells, bacterial internalization is not requi red for the signaling mechanisms that induce PMN movement. Here, we sought to determine which S, typhimurium factors and intestinal epithelial signali ng pathways elicit the production of PMN chemoattractants by enterocytes. O ur results suggest that S. typhimurium activates a protein kinase C-depende nt signal transduction pathway that orchestrates transepithelial PMN moveme nt. We show that the type ill effector protein, SipA, is not only necessary but is sufficient to induce this proinflammatory response in epithelial ce lls. Our results force us to reconsider the long-held view that Salmonella effector proteins must be directly delivered into host cells from bacterial cells.