Waging war against uropathogenic Escherichia coli: winning back the urinary tract

Abstract

Urinary tract infection (UTI) caused by uropathogenic Escherichia coli (UPEC) is a substantial economic and societal burden-a formidable public health issue. Symptomatic UTI causes significant discomfort in infected patients, results in lost productivity, predisposes individuals to more serious infections, and usually necessitates antibiotic therapy. There is no licensed vaccine available for prevention of UTI in humans in the United States, likely due to the challenge of targeting a relatively heterogeneous group of pathogenic strains in a unique physiological niche. Despite significant advances in the understanding of UPEC biology, mechanistic details regarding the host response to UTI and full comprehension of genetic loci that influence susceptibility require additional work. Currently, there is an appreciation for the role of classic innate immune responses-from pattern receptor recognition to recruitment of phagocytic cells-that occur during UPEC-mediated UTI. There is, however, a clear disconnect regarding how factors involved in the innate immune response to UPEC stimulate acquired immunity that facilitates enhanced clearance upon reinfection. Unraveling the molecular details of this process is vital in the development of a successful vaccine for prevention of human UTI. Here, we survey the current understanding of host responses to UPEC-mediated UTI with an eye on molecular and cellular factors whose activity may be harnessed by a vaccine that stimulates lasting and sterilizing immunity.

Figures

FIG. 1.

Histological and schematic views of the murine bladder. (A) Hematoxylin and eosin (H&E)-stained section from a healthy wild-type C57BL/6 female mouse. Magnification, ×200. Scale bar, 100 μm. (B) Schematic representation of bladder physiology shown in panel A. Umbrella cells line the luminal surface of the transitional epithelium. The basal side of the umbrella cell layer consists of intermediate and basal cells, followed by the lamina propria, the primary site of edema and inflammation during UTI. (C and D) H&E-stained sections from wild-type C57BL/6 mice that were either left untreated (C) or infected for 48 h (D). Note the severe inflammation and edema in the lamina propria of the infected animal. Magnification, ×40. Scale bar, 500 μm.