TIME-COURSE AND HOST RESPONSES TO ESCHERICHIA-COLI URINARY-TRACT INFECTION IN GENETICALLY DISTINCT MOUSE STRAINS

Recurrent urinary tract infections (UTIs) are a significant clinical p roblem for many women; however, host susceptibility factors have not b een completely defined. The mouse model of induced UTI provides an exp erimental environment in which to identify specific host characteristi cs that are important in initial bacterial colonization of the urinary tract and in resolution of an infection. This study examined initial susceptibility, bacterial clearance, and host defense mechanisms durin g induction and resolution of Escherichia coli UTIs in genetically dis tinct strains of mice. Of the ten inbred strains tested, six (BALB/c, C3H/HeN, C57BL/6, DBA.1, DBA.2, and AKR) showed progressive resolution of bladder infections over a 14-day period. A constant, low-level bla dder infection was observed in SWR and SJL mice. High bladder infectio n levels persisted over the 14-day study period in C3H/HeJ and Q3H/OuJ mice, Kidney infection levels generally correlated with bladder infec tion levels, especially in C3H/HeJ and C3H/OuJ mice, the two most susc eptible strains, in which infections became more severe with time afte r challenge. The degree of inflammation in bladder and kidneys, as wel l as antibody-forming cell responses, positively correlated with infec tion intensity in all strains except C3H/HeJ, which had minimal inflam mation despite high infection levels. These results demonstrate two im portant aspects of host defense against UTI, First, the innate immune response to an infection in the bladder or kidneys consists primarily of local inflammation, which is followed by an adaptive response chara cterized in part by an antibody response to the infecting bacteria. Se cond, a UTI will be spontaneously resolved in most cases; however, in mice with specific genetic backgrounds, a UTI can persist for an exten ded length of time. The latter result strongly suggests that the prese nce or absence of specific host genes will determine how effectively a n E, coli UTI will be resolved.