Abstract
BackgroundEpidemiologic studies show a strong association between Ureaplasmas and urogenital tract disease in humans. Since healthy humans can be colonized with Ureaplasmas, its role as a pathogen remains controversial. In order to begin to define the role of the host in disease, we developed a rodent model of urinary tract infection (UTI) using Fischer 344 (F344) rats. Animals were inoculated with sterile broth, 101, 103, 105, 107, or 109 log CFU of a rat-adapted strain of Ureaplasma parvum.ResultsInfected animals exhibited two distinct profiles, asymptomatic UTI and UTI complicated with struvite urolithiasis. Inoculum dose of U. parvum affected the incidence of UTI, and 50% to 57% of animals inoculated with ≥ 107 CFU of U. parvum remained infected (p < 0.04). However, inoculum dose did not influence immune response to U. parvum. Asymptomatic UTI was characterized by a minimal immune response that was predominantly monocytic and lymphocytic, with limited lesions, and elevated urinary levels of IFN-γ, IL-18 and MCP-1 (P ≤ 0.02). UTI complicated with struvite formation was characterized by an exaggerated immune response that was mostly neutrophilic (P ≤ 0.0001), with lesions that showed extensive uroepithelial hyperplasia (P ≤ 0.0001), and a predominance of IL-1α, IL-1β, and GRO/KC in the urine (P ≤ 0.02). Animals with asymptomatic UTI also had a significantly high rate of kidney infection (P ≤ 0.0005).ConclusionComplications associated with U. parvum infection are primarily dependent upon host-specific factors rather than Ureaplasma microbial load. The immune response in F344 rats is similar to that which occurs in humans with ureaplasmal associated disease. Therefore, this model of infection is a useful tool for elucidating U. parvum-host interactions that confer UTI and disease.
Highlights
Epidemiologic studies show a strong association between Ureaplasmas and urogenital tract disease in humans
Ureaplasmas can be isolated from healthy individuals, epidemiologic studies have shown a strong association between Ureaplasmas and various diseases including non-gonococcal urethritis (NGU), bacterial vaginosis, infertility, prostatitis, epididymitis, urinary tract infection (UTI), nephrolithiasis, postpartum endometritis, chorioamnionitis, spontaneous abortion, premature birth, stillbirth and neonatal pneumonia [1,2,3,4]
We showed that the inbred rat strain Fischer 344 (F344) is susceptible to UTI induced by a rat adapted strain of Ureaplasma parvum isolated from the urine of a patient with recurrent UTI [13]
Summary
Epidemiologic studies show a strong association between Ureaplasmas and urogenital tract disease in humans. In order to begin to define the role of the host in disease, we developed a rodent model of urinary tract infection (UTI) using Fischer 344 (F344) rats. As part of that study, we found that 60% of infected F344 rats developed struvite uroliths, which were associated with an exaggerated inflammatory response that is similar to what has been reported in other disease states caused by Ureaplasma infection [1,5,6,11,12]. The other 40% of F344 rats developed uncomplicated UTI that was characterized by low concentrations of pro-inflammatory cytokines in urine as well as mild to moderate lesions in the lower urinary tract. Since F344 rats are an inbred strain, this particular infection model would be useful for identifying the host/Ureaplasma interactions that confer disease or asymptomatic infection without confounding variables that would be introduced by genetic variability
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