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Infection and Immunity, October 2009, p. 4265-4274, Vol. 77, No. 10
0019-9567/09/$08.00+0 doi:10.1128/IAI.00458-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Complicated Urinary Tract Infection Is Associated with Uroepithelial Expression of Proinflammatory Protein S100A8
,
Leticia Reyes,1*
Sophie Alvarez,2,
Ayman Allam,1
Mary Reinhard,1 and
Mary B. Brown1
University of Florida, College of Veterinary Medicine, Department of Infectious Diseases and Pathology, P.O. Box 110880, Gainesville, Florida 32611-0880,1 Interdisciplinary Center for Biotechnology Research, University of Florida, Gainesville, Florida 326112
Received 23 April 2009/ Returned for modification 5 June 2009/ Accepted 30 July 2009
F344 rats chronically infected with Ureaplasma parvum develop two distinct profiles: asymptomatic urinary tract infection (UTI) and UTI complicated by struvite urolithiasis. To identify factors that affect disease outcome, we characterized the temporal host immune response during infection by histopathologic analysis and in situ localization of U. parvum. We also used differential quantitative proteomics to identify distinguishing host cellular responses associated with complicated UTI. In animals in which microbial colonization was limited to the mucosal surface, inflammation was indistinguishable from that which occurred in sham-inoculated controls, and the inflammation resolved by 72 h postinoculation (p.i.) in both groups. However, inflammation persisted in animals with microbial colonization that extended into the deeper layers of the submucosa. Proteome profiling showed that bladder tissues from animals with complicated UTIs had significant increases (P < 0.01) in proteins involved in apoptosis, oxidative stress, and inflammation. Animals with complicated UTIs (2 weeks p.i.) had the highest concentrations of the proinflammatory protein S100A8 (P 
0.005) in bladder tissues, and the levels of S100A8 positively correlated with those of proinflammatory cytokines GRO/KC (P 0.003) and interleukin-1
(P 0.03) in urine. The bladder uroepithelium was a prominent cell source of S100A8-S100A9 in animals with complicated UTIs (2 weeks p.i.), which was not detected in animals with asymptomatic UTIs (2 weeks p.i.) or in any bladder tissues harvested at earlier p.i. time points. Based on these results, we surmise that invasive colonization of the bladder triggers chronic inflammation and immune dysregulation, which may be critical to struvite formation.
* Corresponding author. Mailing address: University of Florida, College of Veterinary Medicine, Department of Infectious Diseases & Pathology, P.O. Box 110880, Gainesville, FL 32611-0880. Phone: (352) 294-4090, ext. 3990. Fax: (352) 846-2781. E-mail: lreyes{at}ufl.edu
Published ahead of print on 10 August 2009.
Supplemental material for this article may be found at http://iai.asm.org/.
Present address: Donald Danforth Plant Science Center, 975 N. Warson Rd., St. Louis, MO 63132.
Infection and Immunity, October 2009, p. 4265-4274, Vol. 77, No. 10
0019-9567/09/$08.00+0 doi:10.1128/IAI.00458-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
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