Estrogenic Modulation of Uropathogenic Escherichia coli Infection Pathogenesis in a Murine Menopause Model
| Autor: | Caihong Wang, Emily Ma, Bin Cao, Indira U. Mysorekar, Jane W. Symington |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Bacteriuria
medicine.drug_class Ovariectomy Immunology Biology urologic and male genital diseases Microbiology Proinflammatory cytokine Pathogenesis Mice medicine Animals Uropathogenic Escherichia coli Urothelium Escherichia coli Infections Escherichia coli infection Drug Implants Inflammation Host Response and Inflammation Estradiol Interleukin-6 Estrogens bacterial infections and mycoses medicine.disease United States female genital diseases and pregnancy complications Mice Inbred C57BL Menopause Infectious Diseases Estrogen Delayed-Action Preparations Urinary Tract Infections Ovariectomized rat Female Parasitology |
| Zdroj: | Infection and Immunity. 81:733-739 |
| ISSN: | 1098-5522 0019-9567 |
| DOI: | 10.1128/iai.01234-12 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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