CVI Accepts, published online ahead of print on 19 November 2008
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Clin. Vaccine Immunol. doi:10.1128/CVI.00323-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Abnormal Immunological Profile and Vaginal Microbiota in Women Prone to Urinary Tract Infections

Pirkka V. Kirjavainen*, Stephen Pautler, Miren L. Baroja, Kingsley Anukam, Kate Crowley, Kristine Carter, and Gregor Reid

Canadian Research and Development Centre for Probiotics, Lawson Health Research Institute, and Departments of Microbiology and Immunology, and Urology/Surgery, The University of Western Ontario, London, Ontario, Canada; Department of Clinical Nutrition, Food and Health Research Centre, School of Public Health and Clinical Nutrition, University of Kuopio, Kuopio, Finland

* To whom correspondence should be addressed. Email: pirkka.kirjavainen{at}uku.fi.


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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 defence and further explored the linkage to vaginal microbiota. For this purpose we compared vaginal, urine and blood samples collected during disease free period from 22 women with recurrent UTI and 17 controls. In UTI prone women IL-12 production was significantly (p<0.05) enhanced in peripheral monocytes and myeloid dendritic cells (DCs) whether measured in relative numbers of IL-12 producing cells or 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 similarly in the UTI group as in controls. In vaginal mucosa, UTI prone women had lower concentration of tissue repair-associated vascular endothelial growth factor (VEGF) (p=0.006) and less often 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 lactobacillus-morphotype diminished, composition with abnormally high (>3) mean Nugent score of 4.6 as opposed to 1.7 in controls (p=0.003). Normal lactobacillus composition was associated with increased IL-17 and VEGF concentrations in vaginal mucosa. In conclusion, immunological defects and persistently aberrant microbiota, lack of lactobacilli in particular, may contribute to the susceptibility to recurrent UTI. Further studies on antigen presenting cell function and T-cell activation in recurrent UTI are called for.