Escherichia coli cytotoxic necrotizing factor-1 (CNF-1) increases the adherence to epithelia and the oxidative burst of human polymorphonuclear leukocytes but decreases bacteria phagocytosis

Recruitment of polymorphonuclear leukocytes (PMNL) is a hallmark of both ur inary and digestive infections caused by Escherichia coli, Cytotoxic necrot izing factor 1 (CNF-1) is a toxin produced by uropathogenic E. coli strains that mediates its effects via the activation of small GTP-binding proteins . However, the role and the consequences of CNF-1 on PMNL physiology remain largely unknown, In this study, we provide evidence that CNF-1 dramaticall y affects the PMNL cytoskeleton architecture by inducing an increased conte nt of F-actin, Furthermore, we demonstrate that CNF-1 increases functional features of PMNL, such as superoxide generation and adherence on epithelial T84 monolayers, but significantly decreases their phagocytic function. Our results suggest that CNF-1 may behave as a virulence factor in urinary or digestive infection by stimulating PMNL cytotoxicity as a result of its enh ancing effect on their adherence to epithelial cells as well as the product ion of radical oxygen products. Moreover, the decreased phagocytosis of PMN L induced by CNF-1 likely facilitates growth of bacteria. In these conditio ns, CNF-1 would intervene in the initiation and in the perpetuation of the inflammatory process.