title: Protein-based profiling of the immune response to uropathogenic Escherichia coli in adult patients immediately following hospital admission for acute cystitis.
abstract: Urinary tract infections (UTIs) caused by uropathogenic Escherichia coli (UPEC) are common infections in humans. Despite the substantial healthcare cost represented by these infections, the human immune response associated with the infection immediately following the onset of symptoms in patients remains largely undefined. We performed a prospective study aimed at defining the milieu of urinary cytokines in adult inpatients in the 24-48 h period immediately following hospital admission for acute cystitis due to UPEC. Urine samples, analyzed using 27-target multiplex protein assays, were used to generate immune profiles for patients and compared to age- and gender-matched healthy controls. The levels of multiple pro-inflammatory cytokines were significantly elevated in urine as a result of infection, an observation consistent with prior findings in murine models and clinical literature. We also identified significant responses for several novel factors not previously associated with the human response to UTI, including Interleukin (IL)-4, IL-7, IL-9, IL-17A, eotaxin, Granulocyte-macrophage colony-stimulating factor (GM-CSF) and several growth factors. These data establish crucial parallels between the human immune response to UPEC and murine model UTI studies, and emphasize the complex but poorly defined nature of the human immune response to UPEC, particularly in the immediate period following the onset of symptoms for acute cystitis.
authors.affiliation: Department of Health, Pathology Queensland, Queensland Government, Gold Coast University Hospital, Gold Coast, Queensland 4211, Australia.
authors.forename: Lana
authors.initials: L
authors.lastname: Sundac
authors.affiliation: School of Medical Science, and Menzies Health Institute Queensland, Griffith University, Gold Coast Campus, Gold Coast, Queensland 4222, Australia.
authors.forename: Samantha J
authors.initials: SJ
authors.lastname: Dando
authors.affiliation: School of Medical Science, and Menzies Health Institute Queensland, Griffith University, Gold Coast Campus, Gold Coast, Queensland 4222, Australia.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Sullivan
authors.affiliation: Department of Health, Pathology Queensland, Queensland Government, Gold Coast University Hospital, Gold Coast, Queensland 4211, Australia.
authors.forename: Petra
authors.initials: P
authors.lastname: Derrington
authors.affiliation: Department of Health, Pathology Queensland, Queensland Government, Gold Coast University Hospital, Gold Coast, Queensland 4211, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Gerrard
authors.affiliation: School of Medical Science, and Menzies Health Institute Queensland, Griffith University, Gold Coast Campus, Gold Coast, Queensland 4222, Australia g.ulett@griffith.edu.au.
authors.forename: Glen C
authors.initials: GC
authors.lastname: Ulett
mesh_terms: D000208:Acute Disease; D000328:Adult; D003556:Cystitis / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D016207:Cytokines / Q000378:metabolism; D004927:Escherichia coli Infections / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D006760:Hospitalization; D054884:Host-Pathogen Interactions; D006801:Humans; D020543:Proteome; D040901:Proteomics / Q000379:methods; D056689:Uropathogenic Escherichia coli / Q000276:immunology*
chemical_list: D016207:Cytokines; D020543:Proteome
keywords: bacterial pathogenesis; cystitis; host response; immune response; urinary tract infection; uropathogenic Escherichia coli