Editors' ChoiceInfectious Disease

Pentraxin 3 Sends Urinary Tract Infection Down the Drain

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Science Translational Medicine  14 May 2014:
Vol. 6, Issue 236, pp. 236ec86
DOI: 10.1126/scitranslmed.3009309

When it comes to treating urinary tract infections (UTIs), sometimes drinking cranberry juice just doesn’t cut it. Indeed, UTIs can have serious downstream effects, including renal failure and septic shock. The body has built-in defenses against UTIs, including the anatomy of the urinary tract and the flushing action of urine, mucins, and antimicrobial peptides, which eliminate contaminating bacteria. If these defenses fail, there is another level of protection in place: Epithelial cells can recognize microbial products, resulting in the generation of mediators that both recruit phagocytes to the site of infection and enhance their antimicrobial effector function. Pentraxins (PTXs) are soluble pattern-recognition receptors produced during inflammation. Diverse myeloid and nonmyeloid cells produce PTX3, which acts as an opsonin favoring phagocyte microbial ingestion. However, the role of PTX3 in the control of UTIs and mediating human UTI pathogenesis remains unknown.

Jailion et al. detected high levels of PTX3 in the urine and blood in mice and people infected with uropathogenic Escherichia coli (UPEC). Mouse Ptx3 deficiency resulted in higher bacterial burden in the bladder and kidney as well as increased neutrophil recruitment, production of chemokine, and tissue damage when compared with that in wild-type mice. The primary sources of PTX3 in the urinary tract were uroepithelial cells and leukocytes recruited into the urinary tract after infection. The authors observed that PTX3 promoted both UPEC uptake and phagosomal maturation by neutrophils. Interestingly, there were significant differences in PTX3 levels in the urine of UTI patients, with varying severity. Indeed, genetic analysis of UTI-prone patients indicated that PTX3 polymorphisms were associated with susceptibility to acute pyelonephritis. The authors also suggested a direct correlation between PTX3 levels in the urine and the magnitude of infection, which indicates that PTX3 may be considered as a potential biomarker for UTIs.

The role of PTX3 in the pathogenesis of UTI presented in this study greatly enhances our understanding of urinary tract infection. These results highlight the possibility of therapeutic opportunities to improve immune competence and microbial clearance in patients with severe UTI.

S. Jailon et al., The humoral pattern recognition molecule PTX3 is a key component of innate immunity against urinary tract infection. Immunity 40, 621–632 (2014). [Abstract]

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