Editors' ChoiceIMMUNITY

Mast Cells Help Bacteria Hang Out After the Party

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Science Translational Medicine  06 Mar 2013:
Vol. 5, Issue 175, pp. 175ec39
DOI: 10.1126/scitranslmed.3006040

No one likes to go home after a good party. Bacteria feel the same way after causing a good infection, but what happens next often depends on the host and how far you push your luck. With urinary tract infections, patients are pretty accommodating hosts after the fact and commonly choose not to mount a pathogen-specific immune response unless the kidney is also involved. As a result, bacteria persist in low numbers within the bladder epithelium, and recurrent infections are often caused by the same bacterial strain.

Chan and colleagues wanted to understand the mechanism of the impaired antibody response to bladder infection as a stepping stone to vaccine development. Using a mouse model of uropathogenic Escherichia coli (UPEC)–induced urinary tract infection, the investigators identified a surge of the anti-inflammatory cytokine interleukin 10 (IL-10) in the bladder just hours after infection that fit with the observed lack of antibodies after bladder infections. In IL-10–deficient mice, antibodies were formed after bladder or kidney infection, suggesting that IL-10 was linked to suppression of antibody responses in the bladder. The researchers then performed an elegant series of experiments that showed that mast cells were the major source of IL-10 in the bladder and that suppression of adaptive immunity was dependent on both mast cells and IL-10. Specifically, both mice lacking mast cells and mice with IL-10–deficient mast cells produced high amounts of antibodies to UPEC after bladder infection and increased clearance of UPEC bacteria from the bladder epithelium was observed.

This study substantially adds to our understanding of how lower urinary tract infections persist and recur in the bladder and why specific antibodies to UPEC and other urinary tract pathogens fail to develop in most patients. From a broader perspective, it is intriguing to learn that the bladder, similar to the gut, has specialized mechanisms to limit immune responses at the mucosal surface, which may allow microbes to superficially colonize the epithelium. These data need to be considered in planning a vaccine if we want to stop UPEC from being the life of the party.

C. Y. Chan et al., Mast cell interleukin-10 drives localized tolerance in chronic bladder infection. Immunity 38, 349–359 (2013). [Abstract]

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