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Clinical and Vaccine Immunology, January 2009, p. 29-36, Vol. 16, No. 1
1071-412X/09/$08.00+0     doi:10.1128/CVI.00323-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

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

Pirkka V. Kirjavainen,1,2* Stephen Pautler,3 Miren L. Baroja,1 Kingsley Anukam,1 Kate Crowley,1 Kristine Carter,3 and Gregor Reid1,3,4

Canadian Research and Development Centre for Probiotics, Lawson Health Research Institute,1 Departments of Microbiology and Immunology,4 Urology/Surgery, The University of Western Ontario, London, Ontario, Canada,3 Department of Clinical Nutrition, Food and Health Research Centre, School of Public Health and Clinical Nutrition, University of Kuopio, Kuopio, Finland2

Received 2 September 2008/ Returned for modification 17 October 2008/ Accepted 4 November 2008

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.

* Corresponding author. Mailing address: Department of Clinical Nutrition, Food and Health Research Centre, School of Public Health and Clinical Nutrition, University of Kuopio, Kuopio, Finland. Phone: 358-40-355-3590. Fax: 358-17-162785. E-mail: pirkka.kirjavainen{at}uku.fi

{triangledown} Published ahead of print on 19 November 2008.

Clinical and Vaccine Immunology, January 2009, p. 29-36, Vol. 16, No. 1
1071-412X/09/$08.00+0     doi:10.1128/CVI.00323-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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