title: Escherichia coli type 1 pili trigger late IL-8 production by neutrophil-like differentiated PLB-985 cells through a Src family kinase- and MAPK-dependent mechanism.
abstract: The innate immune response to enteropathogenic bacteria includes chemokine-induced polymorphonuclear neutrophil (PMN) migration across mucosal epithelia leading to bacterial clearance and resolution of infection. Among these bacteria, diffusely adherent Escherichia coli expressing Afa/Dr fimbriae (Afa/Dr DAEC), causing childhood diarrhea, can promote IL-8-dependent PMN transmigration across cultured intestinal epithelial cell monolayers via MAPK pathway activation. However, interactions between PMN and Afa/Dr DAEC are poorly documented and constitute the aim of the present study. Using the human PLB-985 cell line differentiated into fully mature PMN, we described the coordinated response to various E. coli. The rapid and strong release of reactive oxygen species and preformed intragranular mediators (myeloperoxidase and IL-8) is followed by a later TNF-alpha, IL-1beta, and IL-8 synthesis. The use of wild-type (IH11128, C1845, LF82), control (AAEC185), and recombinant (AAEC185 bearing Dr or F1845 fimbriae, AdLF82, or type 1 pili) bacterial strains allowed us to demonstrate that late IL-8 hyperproduction is triggered by type 1 pili but not by Dr or F1845 fimbriae; MAPKs (p38, ERK, Src) and NF-kappaB activations are implicated in this response. Thus, in the course of Afa/Dr DAEC intestinal infection, epithelium- and neutrophil-derived IL-8 could, at least in part, control the flow of neutrophils through the lamina propria. Afa/Dr DAEC-induced IL-8 hyperproduction by PMN might thus be important for inducing and perpetuating local inflammation, and this self-amplifying loop might play a role in the pathogenesis of inflammatory bowel diseases such as Crohn's disease.
authors.affiliation: INSERM, UMR756, Signalisation et Physiopathologie des Cellules Epithéliales, and Université Paris-Sud XI, Faculté de Pharmacie, Châtenay-Malabry, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Sémiramoth
authors.forename: Aude
authors.initials: A
authors.lastname: Gleizes
authors.forename: Isabelle
authors.initials: I
authors.lastname: Turbica
authors.forename: Catherine
authors.initials: C
authors.lastname: Sandré
authors.forename: Roseline
authors.initials: R
authors.lastname: Gorges
authors.forename: Imad
authors.initials: I
authors.lastname: Kansau
authors.forename: Alain
authors.initials: A
authors.lastname: Servin
authors.forename: Sylvie
authors.initials: S
authors.lastname: Chollet-Martin
mesh_terms: D015703:Antigens, CD / Q000276:immunology; D001422:Bacterial Adhesion; D039481:CD11b Antigen / Q000276:immunology; D018821:CD18 Antigens / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000276:immunology; D002454:Cell Differentiation; D004926:Escherichia coli / Q000166:cytology / Q000276:immunology*; D010861:Fimbriae, Bacterial / Q000276:immunology*; D058851:GPI-Linked Proteins; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009504:Neutrophils / Q000166:cytology / Q000201:enzymology* / Q000382:microbiology; D009195:Peroxidase / Q000378:metabolism; D016897:Respiratory Burst / Q000276:immunology; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D039481:CD11b Antigen; D018821:CD18 Antigens; C504117:CEACAM6 protein, human; D015815:Cell Adhesion Molecules; D058851:GPI-Linked Proteins; C509295:ITGAM protein, human; D016209:Interleukin-8; D008070:Lipopolysaccharides; D009195:Peroxidase; D019061:src-Family Kinases; D020928:Mitogen-Activated Protein Kinases