Editors' ChoiceURINARY TRACT INFECTION

The Calming Effect of Escherichia coli

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Science Translational Medicine  18 Apr 2012:
Vol. 4, Issue 130, pp. 130ec66
DOI: 10.1126/scitranslmed.3004135

Uropathogenic Escherichia coli (UPEC) bacteria are a leading cause of urinary tract infections (UTIs), which are among the most common infections in the developed world. When untreated, UTIs can spread from the urethra and bladder to the kidney and beyond with severe consequences. Loughman and Hunstad now report that UPEC induce expression of a host enzyme that attenuates our innate immune response, giving some specificity to many previous reports that UPEC suppress human immune and inflammatory responses that would otherwise act to fight these bacteria.

Using a mouse model, the authors showed that expression of indoleamine 2,3-dioxygenase (IDO)—an enzyme previously shown to have immunomodulatory effects—was induced in bladder cells infected with UPEC strains. This effect is specific for UPEC because levels of the RNA transcript encoded by the IDO gene Ido1 were significantly higher in bladder cells from UPEC-infected mice as compared with those infected with a nonpathogenic E. coli strain. Subsequent experiments also verified a UPEC-induced proinflammatory response in mice that cannot produce IDO, coupled with reduced survival of bacteria. Additionally, UPEC induced IDO expression in human neutrophil and bladder cells. It appears that without IDO, bladder cells quickly initiate an inflammatory response to pathogenic bacteria; however, UPEC strains (but not all E. coli) cause bladder cells to produce IDO that can sufficiently minimize this inflammation to facilitate bacterial survival. In short, UPEC trick the host into calming its own immune response—a maneuver that allows for a more severe infection.

In the future, it will be important to determine the specific mechanism of IDO induction by UPEC and how IDO activity curtails neutrophil responses. Such information may allow for the development of a more targeted therapeutic approach to cure and prevent UTIs. One of the current mysteries surrounding UTIs is the high incidence of secondary infection within 6 months to a year after the initial infection in women. Simply reducing this UTI recurrence rate would have large health benefits. Do some UPEC bacteria remain, protected by IDO, as the acute infection subsides? A greater understanding of the specific interactions between UPEC and human cells throughout the course of infection will be useful for treating this disease more effectively.

J. A. Loughman, D. A. Hunstad, Induction of indoleamine 2,3-dioxygenase by uropathogenic bacteria attenuates innate responses to epithelial infection. J. Infect. Dis. 3 April 2012 (10.1093/infdis/jis280). [Abstract]

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