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Published on: September 15, 2017
Different inflammatory responses are associated with Ureaplasma parvum-induced UTI and urolith formation
Leticia Reyes1, Mary Reinhard, Mary B Brown
1Department of Infectious Disease & Pathology, College of Veterinary Medicine, University of Florida, Gainesville, FL, USA. lreyes@ufl.edu
Background:
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, 10(1), 10(3), 10(5), 10(7), or 10(9) log CFU of a rat-adapted strain of Ureaplasma parvum.
Results:
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 >or= 10(7) 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-gamma, IL-18 and MCP-1 (P
Conclusion:
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.
Insights
Host factors, not bacterial load, dictate Ureaplasma parvum infection outcomes. This study in Fischer 344 rats reveals distinct immune responses correlating with asymptomatic urinary tract infections (UTI) or complicated UTI with urolithiasis, offering insights into Ureaplasma-host interactions.
Area of Science:
- Microbiology
- Immunology
- Urology
Background:
- Epidemiologic studies link Ureaplasmas to urogenital tract disease, but their pathogenic role is debated due to asymptomatic colonization in healthy individuals.
- A Fischer 344 (F344) rat model was developed to investigate host factors in Ureaplasma-associated urinary tract infections (UTI).
Purpose of the Study:
- To define the role of the host in Ureaplasma parvum-induced UTI.
- To characterize the immune response and disease profiles in a rodent model of Ureaplasma infection.
Main Methods:
- Fischer 344 rats were inoculated with varying doses (10^1 to 10^9 CFU) of a rat-adapted Ureaplasma parvum strain.
- Animals were assessed for UTI development, urolithiasis, and immune responses, including cytokine profiles and cellular infiltration.
Main Results:
- Inoculum dose influenced UTI incidence, with higher doses (> or = 10^7 CFU) leading to persistent infection.
- Two distinct UTI profiles emerged: asymptomatic UTI with monocytic/lymphocytic response and elevated IFN-gamma, IL-18, MCP-1; and complicated UTI with struvite urolithiasis, neutrophilic response, and elevated IL-1 alpha, IL-1 beta, GRO/KC.
- Asymptomatic UTI was associated with a higher rate of kidney infection.
Conclusions:
- Complications of Ureaplasma parvum infection are primarily determined by host-specific factors, not microbial load.
- The immune response observed in F344 rats mirrors human responses in ureaplasmal-associated diseases.
- This rodent model is valuable for studying Ureaplasma parvum-host interactions in UTI pathogenesis.
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