title: Uropathogenic Escherichia coli as a model of host-parasite interaction.
abstract: Resistance to mucosal infection varies greatly in the population, but the molecular basis of disease susceptibility is often unknown. Studies of host-pathogen infections are helpful to identify virulence factors, which characterise disease isolates, and successful defence strategies of hosts that resist infection. In the urinary tract infection (UTI) model, we have identified crucial steps in the pathogen-activated innate host response, and studied the genetic control of these activation steps. Furthermore, genetic variation in the innate host-response defence is investigated as a basis of disease susceptibility. The Toll-like receptor 4 (TLR4) controls initial mucosal response to uropathogenic Escherichia coli (UPEC). Bacterial TLR4 activation in epithelial cells leads to chemokine secretion and neutrophil recruitment and TLR4 mutant mice develop an asymptomatic carrier state. The chemokine receptor CXCR1 determines the efficiency of neutrophil migration and activation, and thus of bacterial clearance. CXCR1 mutant mice become bacteremic and develop renal scars and studies in UTI prone children have detected low CXCR1 expression, suggesting that CXCR1 is also essential for human disease susceptibility.
authors.affiliation: Department of Microbiology, Immunology and Glycobiology, Institute of Laboratory Medicine, Lund University, Lund, Sweden. Catharina.Svanborg@mig.lu.se
authors.forename: Catharina
authors.initials: C
authors.lastname: Svanborg
authors.forename: Göran
authors.initials: G
authors.lastname: Bergsten
authors.forename: Hans
authors.initials: H
authors.lastname: Fischer
authors.forename: Gabriela
authors.initials: G
authors.lastname: Godaly
authors.forename: Mattias
authors.initials: M
authors.lastname: Gustafsson
authors.forename: Diana
authors.initials: D
authors.lastname: Karpman
authors.forename: Ann-Charlotte
authors.initials: AC
authors.lastname: Lundstedt
authors.forename: Bryndis
authors.initials: B
authors.lastname: Ragnarsdottir
authors.forename: Majlis
authors.initials: M
authors.lastname: Svensson
authors.forename: Björn
authors.initials: B
authors.lastname: Wullt
mesh_terms: D000818:Animals; D004198:Disease Susceptibility; D004926:Escherichia coli / Q000276:immunology* / Q000472:pathogenicity*; D004927:Escherichia coli Infections / Q000276:immunology* / Q000382:microbiology*; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D051379:Mice; D009092:Mucous Membrane / Q000276:immunology / Q000382:microbiology; D009504:Neutrophils / Q000276:immunology; D023062:Receptors, Interleukin-8A / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000276:immunology; D014551:Urinary Tract / Q000382:microbiology; D014552:Urinary Tract Infections / Q000276:immunology* / Q000382:microbiology*
chemical_list: D023062:Receptors, Interleukin-8A; D051197:Toll-Like Receptor 4