NDLI: Estrogenic Modulation of Uropathogenic Escherichia coli Infection Pathogenesis in a Murine Menopause Model

Content Provider	PubMed Central
Author	Wang, Caihong Symington, Jane W. Ma, Emily Cao, Bin Mysorekar, Indira U.
Editor	Bäumler, A. J.
Copyright Year	2013
Abstract	Recurrent urinary tract infections (UTIs), primarily caused by uropathogenic Escherichia coli (UPEC), annually affect over 13 million patients in the United States. Menopausal women are disproportionally susceptible, suggesting estrogen deficiency is a significant risk factor for chronic and recurrent UTI. How estrogen status governs susceptibility to UTIs remains unknown, and whether hormone therapy protects against UTIs remains controversial. Here, we used a mouse model of surgical menopause by ovariectomy and demonstrate a protective role for estrogen in UTI pathogenesis. We found that ovariectomized mice had significantly higher bacteriuria, a more robust inflammatory response, and increased production of the proinflammatory cytokine interleukin-6 (IL-6) upon UPEC infection compared to sham-operated controls. We further show that response of the urothelial stem cell niche to infection, normally activated to restore homeostasis after infection, was aberrant in ovariectomized mice with defective superficial urothelial cell differentiation. Finally, UPEC-infected ovariectomized mice showed a significant increase in quiescent intracellular bacterial reservoirs, which reside in the urothelium and can seed recurrent infections. Importantly, this and other ovariectomy-induced outcomes of UTI were reversible upon estrogen supplementation. Together, our findings establish ovariectomized mice as a model for UTIs in menopausal women and pinpoint specific events during course of infection that are most susceptible to estrogen deficiency. These findings have profound implications for the understanding of the role of estrogen and estrogen therapy in bladder health and pathogen defense mechanisms and open the door for prophylaxis for menopausal women with recurrent UTIs.
Related Links	http://dx.doi.org/10.1128/iai.01234-12
Ending Page	739
Page Count	7
Starting Page	733
File Format	PDF
ISSN	00199567
e-ISSN	10985522
Journal	Infection and Immunity
Issue Number	3
Volume Number	81
Language	English
Publisher	American Society for Microbiology
Publisher Date	2013-03-01
Access Restriction	Open
Rights Holder	American Society for Microbiology
Subject Keyword	Immunology Microbiology Parasitology Infectious Diseases Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Infectious Diseases Parasitology Immunology Microbiology

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