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 urinary and digestive infections caused by Escherichia coli. Cytotoxic necrotizing 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 dramatically affects the PMNL cytoskeleton architecture by inducing an increased content 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 enhancing effect on their adherence to epithelial cells as well as the production of radical oxygen products. Moreover, the decreased phagocytosis of PMNL induced by CNF-1 likely facilitates growth of bacteria. In these conditions, CNF-1 would intervene in the initiation and in the perpetuation of the inflammatory process.
Hofman
P
P
Laboratoire d'Anatomie-Pathologique, INSERM U364, Nice, France. hofman@unice.fr
Le Negrate
G
G
Mograbi
B
B
Hofman
V
V
Brest
P
P
Alliana-Schmid
A
A
Flatau
G
G
Boquet
P
P
Rossi
B
B
D000199:Actins / Q000378:metabolism; D001427:Bacterial Toxins / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000187:drug effects; D003603:Cytotoxins / Q000494:pharmacology*; D004847:Epithelial Cells / Q000166:cytology; D004926:Escherichia coli / Q000472:pathogenicity*; D029968:Escherichia coli Proteins; D006801:Humans; D007249:Inflammation / Q000139:chemically induced; D007413:Intestinal Mucosa / Q000166:cytology; D016177:Macrophage-1 Antigen / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects* / Q000382:microbiology / Q000502:physiology / Q000648:ultrastructure; D009895:Opsonin Proteins / Q000494:pharmacology; D010587:Phagocytosis / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D016897:Respiratory Burst / Q000187:drug effects*; D013481:Superoxides / Q000378:metabolism; D014774:Virulence; D015054:Zymosan / Q000494:pharmacology; D020741:rho GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000502:physiology
D000199:Actins; D001427:Bacterial Toxins; D003603:Cytotoxins; D029968:Escherichia coli Proteins; D016177:Macrophage-1 Antigen; D009895:Opsonin Proteins; D017382:Reactive Oxygen Species; C060296:cytotoxic necrotizing factor type 1; D013481:Superoxides; D015054:Zymosan; D020741:rho GTP-Binding Proteins