The fimbriae of enteroaggregative Escherichia coli induce epithelial inflammation in vitro and in a human intestinal xenograft model.
BACKGROUND
Enteroaggregative Escherichia coli (EAEC) are increasingly recognized as an important agent of inflammatory and often persistent diarrhea. Although previous studies report on the inflammatory aspects of EAEC pathogenesis, the mechanisms by which EAEC trigger these events are not well understood.


METHODS
EAEC strains harboring mutations in known EAEC virulence determinants were tested in an in vitro model of transepithelial migration of polymorphonuclear neutrophils (PMNs) and in human intestinal xenografts in severe-combined immunodeficient (SCID-HU-INT) mice, a novel model for studying EAEC disease in vivo.


RESULTS
Expression of aggregative adherence fimbriae (AAFs), the principal adhesins of EAEC, was required for EAEC-induced PMN transepithelial migration in vitro. Moreover, constructed plasmids encoding AAF gene clusters demonstrated that the AAF adhesins are sufficient for triggering this event in a nonpathogenic E. coli background. Furthermore, with use of the SCID-HU-INT mouse model, severe tissue damage and infiltration of inflammatory cells was observed in the human tissue after EAEC infection. These pathological marks were strongly related to AAF expression, thus clearly confirming our in vitro findings.


CONCLUSIONS
The present work establishes EAEC as an important inflammatory pathogen and the AAF adhesins as inducers of potentially detrimental immune responses.
Department of Microbiological Surveillance and Research,  Statens Serum Institut,  Denmark.
Erik J
EJ
Boll
Carsten
C
Struve
Anja
A
Sander
Zachary
Z
Demma
James P
JP
Nataro
Beth A
BA
McCormick
Karen A
KA
Krogfelt
D018830:Adhesins, Escherichia coli / Q000235:genetics / Q000276:immunology*; D000818:Animals; D001422:Bacterial Adhesion / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D003001:Cloning, Molecular; D003967:Diarrhea / Q000276:immunology / Q000382:microbiology*; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000276:immunology*; D004927:Escherichia coli Infections / Q000276:immunology* / Q000382:microbiology; D010861:Fimbriae, Bacterial / Q000276:immunology* / Q000382:microbiology; D006651:Histocytochemistry; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D051379:Mice; D016513:Mice, SCID; D009504:Neutrophils / Q000276:immunology; D014183:Transplantation, Heterologous
D018830:Adhesins, Escherichia coli