Modulation of neutrophil function by a secreted mucinase of Escherichia coli O157:H7.
Escherichia coli O157:H7 is a human enteric pathogen that causes hemorrhagic colitis which can progress to hemolytic uremic syndrome, a severe kidney disease with immune involvement. During infection, E. coli O157:H7 secretes StcE, a metalloprotease that promotes the formation of attaching and effacing lesions and inhibits the complement cascade via cleavage of mucin-type glycoproteins. We found that StcE cleaved the mucin-like, immune cell-restricted glycoproteins CD43 and CD45 on the neutrophil surface and altered neutrophil function. Treatment of human neutrophils with StcE led to increased respiratory burst production and increased cell adhesion. StcE-treated neutrophils exhibited an elongated morphology with defective rear detachment and impaired migration, suggesting that removal of the anti-adhesive capability of CD43 by StcE impairs rear release. Use of zebrafish embryos to model neutrophil migration revealed that StcE induced neutrophil retention in the fin after tissue wounding, suggesting that StcE modulates neutrophil-mediated inflammation in vivo. Neutrophils are crucial innate effectors of the antibacterial immune response and can contribute to severe complications caused by infection with E. coli O157:H7. Our data suggest that the StcE mucinase can play an immunomodulatory role by directly altering neutrophil function during infection. StcE may contribute to inflammation and tissue destruction by mediating inappropriate neutrophil adhesion and activation.
Szabady
Rose L
RL
Department of Medical Microbiology and Immunology, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA.
Lokuta
Mary A
MA
Walters
Kevin B
KB
Huttenlocher
Anna
A
Welch
Rodney A
RA
D000818:Animals; D002448:Cell Adhesion; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte; D004625:Embryo, Nonmammalian / Q000276:immunology / Q000378:metabolism; D019453:Escherichia coli O157 / Q000201:enzymology*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007249:Inflammation; D017493:Leukocyte Common Antigens / Q000378:metabolism; D051917:Leukosialin / Q000378:metabolism; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D018375:Neutrophil Activation; D009504:Neutrophils / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D016897:Respiratory Burst; D015027:Zebrafish / Q000196:embryology / Q000276:immunology / Q000378:metabolism
D029968:Escherichia coli Proteins; D051917:Leukosialin; C465014:SPN protein, human; D017493:Leukocyte Common Antigens; C516769:PTPRC protein, human; D008666:Metalloendopeptidases; C465555:StcE protein, E coli