We have also demonstrated that an antibody-mediated immune response is elicited by an UTI in mice, consistent with results for nonhuman primates (13). 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 characterized in part by an antibody response to the infecting bacteria. Second, a UTI will be spontaneously resolved in most cases; however, in mice with specific genetic backgrounds, a Tioxolone UTI can persist for an extended length of time. The latter result strongly suggests that the presence or absence of specific host genes will determine how effectively an UTI will be resolved. Urinary tract infections (UTIs) are one of the most common conditions seen in main care, hospitals, and extended-care facilities (17). While UTIs can affect both men and women, they are far more prevalent in females. Approximately 50% of adult women report having experienced one or more UTIs, and some of these women will Tioxolone develop a history of repeated infections (17, 18). A number of studies have sought to define characteristics that make this patient populace unusually susceptible to UTIs. Among host factors described thus far are increased numbers of receptors for uropathogenic on vaginal and bladder epithelial cells (23), lowered urinary glycosaminoglycan excretion (19), low levels of cervicovaginal or urinary antibodies to uropathogens (12, 26, 27), hyporesponsiveness to antigens on uropathogenic (14), and specific ABO or Lewis erythrocyte antigen phenotypes (15, 20, 24). Animal Tioxolone models provide a means to evaluate host factors that impact resistance to UTIs. Results from studies of mice and rats have revealed that a genetic component may be important in determining increased UTI susceptibility. A more severe UTI evolves in the SWR and AKR strains than in BALB/c or C57BL/6 strains when mice are inoculated intravesically with (6, 7), and C3H/OuJ and C3H/HeJ mice are significantly less able to handle an UTI than C3H/HeN mice (10). The objectives of the current study were to determine the extent to which the genetic backgrounds of other inbred strains impact induction and resolution of an UTI and to delineate the innate and adaptive immune responses elicited by bladder and kidney infections. Our data on the time course, local inflammatory responses, and antibody-mediated immunity to a UTI induced in different inbred mouse strains show the capacity of mice to resolve an UTI and provide further evidence that a genetic component is associated with host susceptibility and resistance to UTI. MATERIALS AND METHODS Mouse strains. C3H/HeN mice were purchased from Harlan-Sprague Dawley (Indianapolis, Ind.). All other strains were obtained from the Jackson Laboratories (Bar Harbor, Maine). The mouse strains evaluated in this study do not have major, congenital immunodeficiencies, although unresponsiveness or hyporesponsiveness to specific mitogens or antigens has been reported. C3H/HeJ mice are unresponsive to the B-cell mitogen, lipopolysaccharide (21), and DBA.1, DBA.2, SJL, and SWR mice are low responders to the T-cell mitogen phytohemagglutinin (9). Poor responses to protein antigens such as bacteriophage have been reported for AKR and BALB/c mice (16), and DBA.1, DBA.2, and SWR strains have diminished antibody responses to ovomucoid (29). Synthetic antigens composed of amino acid polymers elicit poor antibody responses in DBA.1, DBA.2, C57BL/6, and SJL mice (2). Significant differences between mouse strains have been reported for an immune response to outer membrane proteins. C3H/HeJ and A/J mice have strong responses, while BALB/c mice respond poorly (4). Infection induction and assessment. Mice were infected by intravesical inoculation with 108 1677 CFU delivered in 50 l. Virulence characteristics Rabbit polyclonal to GNRH of this strain include type 1 and P fimbriae, hemolysin, aerobactin,.