Effect of Helicobacter pylori on polymorphonuclear leukocyte migration across polarized T84 epithelial cell monolayers: Role of vacuolating toxin VacA and cag pathogenicity island

Helicobacter pylori infection can induce poly-morphonuclear leukocyte (PMNL ) infiltration of the gastric mucosal which characterizes acute chronic gas tritis, The mechanisms underlying this process are poorly documented. The l ack of an in vitro model has considerably impaired the study of transepithe lial migration of PMNL induced by H. pylori. In the present work, we used c onfluent polarized monolayers of the human intestinal cell line T84 grown o n permeable filters to analyze the epithelial PMNL response induced by brot h culture filtrates (BCFs) and bacterial suspensions from different strains of H. pylori. We have evaluated the role of the vacuolating cytotoxin VacA and of the cag pathogenicity island (PAI) of H. pylori in PMNL migration v ia their effects on T84 epithelial cells. We noted no difference in the rat es of PMNL transepithelial migration after epithelial preincubation with ba cterial suspensions or with BCFs of VacA-negative or VacA-positive H. pylor i strains. In contrast, PMNL transepithelial migration was induced after in cubation of the T84 cells with cag PAI-positive and cagE-positive H. pylori strains. Finally, PMNL migration was correlated with a basolateral secreti on of interleukin-8 by T84 cells, thus creating a subepithelial chemotactic gradient for PMNL. These data provide evidence that the vacuolating cytoto xin VacA is not involved in PMNL transepithelial migration and that the cag PAI, with a pivotal role for the cagE gene, provokes a transcellular signa l across T84 monolayers, inducing a subepithelial PMNL response.