Role of fimbriae‐mediated adherence for neutrophil migration across Escherichia coli‐infected epithelial cell layers

Abstract

SummaryThis study examined the role of P and type 1 fimbriae for neutrophil migration across Escherichia coli-infected uroepithelial cell layers in vitro and for neutrophil recruitment to the urinary tract in vivo. Recombinant E. coli K-12 strains differing in P or type 1 fimbrial expression were used to infect confluent epithelial layers on the underside of transwell inserts. Neutrophils were added to the upper well, and their passage across the epithelial cell layers was quantified. Infection with the P-and type 1-fimbriated recombinant E. coli strains stimulated neutrophil migration to the same extent as a fully virulent clinical E. coli isolate, but the isogenic non-fimbriated vector control strains had no stimulatory effect. The enhancement of neutrophil migration was adhesion dependent; it was inhibited by soluble receptor analogues blocking the binding of P fimbriae to the globoseries of glycosphingolipids or of type 1 fimbriae to mannosylated glycoprotein receptors. P-and type 1-fimbriated E. coli triggered higher interleukin (IL) 8 secretion and expression of functional IL-8 receptors than nonfimbriated controls, and the increase in neutrophil migration across infected cell layers was inhibited by anti-IL-8 antibodies. In a mouse infection model, P-or type 1-fimbriated E. coli stimulated higher chemokine (MIP-2) and neutrophil responses than the non-fimbriated vector controls. The results demonstrated that transformation with the pap or fim DNA sequences is sufficient to convert an E. coli K-12 strain to a host response inducer, and that fimbriation enhances neutrophil recruitment in vitro and in vivo. Epithelial chemokine production provides a molecular link between the fimbriated bacteria that adhere to epithelial cells and tissue inflammation.

How epithelial cells detect danger: aiding the immune response

“…This may well have consequences for the types and expression levels of epithelial receptors or their response. Where bladder epithelial cells respond efficiently to, for instance, lipopolysaccharide (LPS) (1), intestinal epithelial cells are relative tolerant (2). Even within the airways there is a large variation: the epithelial cells lining the lower respiratory tract are from a different embryonic origin than the cells lining the upper respiratory tract and within the nasal cavity one can find specialized olfactory epithelium alongside pseudo-stratified ciliated epithelium and ÔstratifiedÕ epithelium.…”

Integrated regulatory responses of fimB to N -acetylneuraminic (sialic) acid and GlcNAc in Escherichia coli K-12

“…Type 1 fimbriae are proinflammatory, stimulating release of IL-6, IL-8, and tumor necrosis factor ␣, and they act synergistically with other bacterial products such as lipopolysaccharide (8)(9)(10)(11)(12). The adhesin is sufficient for invasion of uroepithelial cells and may contribute to the etiology of the chronic inflammatory diseases, Crohn's disease, and interstitial cystitis (13)(14)(15)(16).…”

The Pathogenesis of Urinary Tract Infections

“…Interleukin-8 is an inflammatory cytokine that promotes neutrophil migration across infected urothelial cells (Godaly et al 1998, Godaly et al 1997. Absence of its receptor CXCR1 has recently been shown to promote bacteraemia within the urinary tract as demonstrated in one study in knockout mice that lacked CXCR1 (Frendeus et al 2001).…”