title: Abnormal immunological profile and vaginal microbiota in women prone to urinary tract infections.
abstract: The host determinants of susceptibility to recurrent urinary tract infections (UTI) are poorly understood. We investigated whether the susceptibility is associated with abnormalities in the immunological defense and further explored the linkage to vaginal microbiota. For this purpose, we compared vaginal, urine, and blood samples collected during a disease-free period from 22 women with recurrent UTI and from 17 controls. In UTI-prone women, interleukin-12 (IL-12) production in peripheral monocytes and myeloid dendritic cells (DCs) was significantly (P < 0.05) enhanced whether measured in relative numbers of IL-12-producing cells or in mean IL-12 production per cell. In contrast, no T-cell polarization was observed. Interestingly, it seemed that the cytokine production of DCs and monocytes did not translate into T-cell activation in the UTI-prone group in a manner similar to that seen with the controls. In vaginal mucosa, UTI-prone women had a lower concentration of tissue repair-associated vascular endothelial growth factor (VEGF) (P = 0.006) and less often had detectable amounts of the chief monocyte and DC chemoattractant, monocyte chemotactic protein 1 (P = 0.005), than the controls. The microbiota of UTI-prone women was characterized by a diminished lactobacillus morphotype composition, with an abnormally high (>3) mean Nugent score of 4.6 compared to 1.7 for the controls (P = 0.003). Normal lactobacillus composition was associated with increased IL-17 and VEGF concentrations in vaginal mucosa. In conclusion, immunological defects and a persistently aberrant microbiota, a lack of lactobacilli in particular, may contribute to susceptibility to recurrent UTI. Further studies of antigen-presenting-cell function and T-cell activation in recurrent UTI are called for.
authors.affiliation: Canadian Research and Development Centre for Probiotics, Lawson Health Research Institute, The University of Western Ontario, London, Ontario, Canada. pirkka.kirjavainen@uku.fi
authors.forename: Pirkka V
authors.initials: PV
authors.lastname: Kirjavainen
authors.forename: Stephen
authors.initials: S
authors.lastname: Pautler
authors.forename: Miren L
authors.initials: ML
authors.lastname: Baroja
authors.forename: Kingsley
authors.initials: K
authors.lastname: Anukam
authors.forename: Kate
authors.initials: K
authors.lastname: Crowley
authors.forename: Kristine
authors.initials: K
authors.lastname: Carter
authors.forename: Gregor
authors.initials: G
authors.lastname: Reid
mesh_terms: D000328:Adult; D000368:Aged; D001419:Bacteria / Q000166:cytology; D001769:Blood / Q000276:immunology; D018932:Chemokine CCL2 / Q000032:analysis; D003713:Dendritic Cells / Q000276:immunology; D004198:Disease Susceptibility / Q000382:microbiology*; D005260:Female; D006801:Humans; D018664:Interleukin-12 / Q000096:biosynthesis; D007778:Lactobacillus / Q000302:isolation & purification; D008213:Lymphocyte Activation; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology; D009092:Mucous Membrane / Q000737:chemistry; D014552:Urinary Tract Infections / Q000276:immunology*; D014556:Urine / Q000737:chemistry; D014621:Vagina / Q000737:chemistry / Q000276:immunology* / Q000382:microbiology*; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
chemical_list: D018932:Chemokine CCL2; D042461:Vascular Endothelial Growth Factor A; D018664:Interleukin-12