Different inflammatory responses are associated with Ureaplasma parvum-induced UTI and urolith formation

Epidemiologic 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.

Infected 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).

Complications 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.