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Infection and Immunity, November 2006, p. 6100-6107, Vol. 74, No. 11
0019-9567/06/$08.00+0 doi:10.1128/IAI.00881-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.
Institute for Molecular Medicine and Experimental Immunology (IMMEI), Bonn, Germany,1 Institut für Molekulare Infektionsbiologie, Würzburg, Germany,2 Department of Pathology, University Clinic of Bonn, Bonn, Germany,3 Anatomical Institute, University of Zurich, Zurich, Switzerland,4 Department of Autoimmune and Inflammatory Diseases, Protein Design Labs Inc., Fremont, California,5 The Weizmann Institute of Science, Department of Immunology, Rehovot, Israel6
Received 2 June 2006/ Returned for modification 24 July 2006/ Accepted 10 August 2006
The role of dendritic cells (DC) in urinary tract infections (UTI) is unknown. These cells contribute directly to the innate defense against various viral and bacterial infections. Here, we studied their role in UTI using an experimental model induced by transurethral instillation of the uropathogenic Escherichia coli (UPEC) strain 536 into C57BL/6 mice. While few DC were found in the uninfected bladder, many had been recruited after 24 h, mostly to the submucosa and uroepithelium. They expressed markers of activation and maturation and exhibited the CD11b+ F4/80+ CD8 Gr-1 myeloid subtype. Also, tumor necrosis factor alpha (TNF-
)- and inducible nitric oxide synthase (iNOS)-producing CD11bINT DC (Tip-DC) were detected, which recently were proposed to be critical in the defense against bacterial infections. However, Tip-DC-deficient CCR2/ mice did not show reduced clearance of UPEC from the infected bladder. Moreover, clearance was also unimpaired in CD11c-DTR mice depleted of all DC by injection of diphtheria toxin. This may be explained by the abundance of granulocytes and of iNOS- and TNF-
-producing non-DC that were able to replace Tip-DC functionality. These findings demonstrate that some of the abundant DC recruited in UTI contributed innate immune effector functions, which were, however, dispensable in the microenvironment of the bladder.
Published ahead of print on 11 September 2006.
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