The immune system may help open the door to recurrent urinary tract infections (UTIs) by overdoing its response to an initial infection, report researchers at Washington University School of Medicine in St. Louis. The findings appear August 12 in the open-access journal PLoS Pathogens.
Using a mouse model, the researchers demonstrated that severe inflammatory responses to an initial UTI cause bladder damage and allow infection to persist longer. In support of this, they found that immunodeficient mice lacking these acute inflammatory responses were protected from chronic bladder infection. Finally, they demonstrated that mice with a history of chronic bladder infection that was subsequently cleared with antibiotic treatment develop persistent immune cell infiltrations within the bladder wall, and these mice are highly susceptible to further UTI.
"We found markers in the mice that may one day help us identify patients vulnerable to recurrent infection and refine our treatment strategies," says lead author Thomas J. Hannan, DVM, PhD. "There were infection-fighting elements in the responses of some mice that we might, for example, be able to promote through vaccines for these patients."
UTIs affect millions of people each year, the authors note. Although antibiotic therapy has historically been helpful, antibiotic resistance is a rapidly increasing concern, according to Scott Hultgren, PhD, director of the Center for Women's Infectious Diseases Research, where the experiments were conduced.
"Women and infants are at greatest risk for having a UTI, and chronic and recurrent infections are common," says Hultgren. "UTIs are estimated to cause around $1.6 billion in medical expenses every year in the United States."
Investigators in Hultgren's laboratory are now collaborating with researchers at the University of Washington and Duke University to see if the mouse results can lead them to markers of vulnerability to recurrent infection in humans.
FINANCIAL DISCLOSURE: This work was supported by National Institutes of Health Grant DK51406 and Office of Research on Women's Health Specialized Center of Research Grant DK64540 (SJH), a Mentored Clinical Scientist Research Career Development Award K08 AI083746 (TJH), and an individual National Research Service Award F32CA108328 and a Pathway to Independence Award K99/R00 DK080643 (IUM). The Siteman Cancer Center is supported in part by NCI Cancer Center Support Grant #P30 CA91842. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
COMPETING INTERESTS: The authors have declared that no competing interests exist.
PLEASE ADD THIS LINK TO THE PUBLISHED ARTICLE IN ONLINE VERSIONS OF YOUR REPORT: http://dx.plos.org/10.1371/journal.ppat.1001042 (link will go live upon embargo lift)
CITATION: Hannan TJ, Mysorekar IU, Hung CS, Isaacson-Schmid ML, Hultgren SJ (2010) Early Severe Inflammatory Responses to Uropathogenic E. coli Predispose to Chronic and Recurrent Urinary Tract Infection. PLoS Pathog 6(8): e1001042. doi:10.1371/journal.ppat.1001042
CONTACT:
Scott Hultgren, Ph.D.
Washington University Medical School
hultgren@borcim.wustl.edu
314 362 6772
Thomas J. Hannan, D.V.M., Ph.D.
Washington University School of Medicine
thannan@wustl.edu
314 362 0368
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