BALB C mice: a novel model for borrelia burgdorferi-induced lyme arthritis

BALB/c mice have been used to study multiple diseases that cause inflammation such as Lyme arthritis, rheumatoid arthritis, and systemic lupus erythematosus. Lyme disease or, more specifically, Lyme arthritis is caused by Borrelia burgdorferi that has disseminated into joint tissues. A spectrum of Lyme disease severity and symptoms has been seen in Lyme disease patients, which suggests that genetics play a role in host response. Inbred mouse strains display the range of arthritis severity seen in patients from the mild arthritis phenotype in C57BL/6 mice to the severe arthritis phenotype in C3H mice. The C3H mouse model develops severe Lyme arthritis that can be attributed to 2 important inflammatory factors: a hypomorphic allele of GusB and hyper production of Type I IFN-induced transcripts. Using SNP-based assessment, the BALB/c mouse was found to be closely related to the C3H mouse; however, the BALB/c mouse does not have the hypomorphic GusB allele. It was hypothesized that the BALB/c mouse, which develops severe, dose-dependent arthritis, would also hyperproduce Type I IFN-related transcripts. This study found that the BALB/c mouse does not develop an IFN profile similar to the C3H mouse. Multiple inflammatory markers were analyzed to compare and contrast BALB/c and C3H mice, and TNFα was determined to be elevated in the BALB/c mouse above the levels in the C3H mouse both in vivo during infection and in vitro using bone marrow-derived macrophages. This suggests an important role of the innate immune response in these mice. Interestingly, peritoneal macrophages derived from BALB/c were able to internalize B. burgdorferi much better than C3H-derived peritoneal macrophages. This suggests an elevated intrinsic response in controlling B. burgdorferi numbers. TNFα blockade has been shown to be beneficial in relieving symptoms in rheumatoid arthritis patients, so it was hypothesized that TNFα blockade in BALB/c mice would reduce Lyme arthritis symptoms. This study did not see any benefit to TNFα blockade in Lyme arthritis reduction. Overall, this study has shown that there are still mechanisms that are yet to be fully understood in the pathogenic relationship between the BALB/c mouse and the spirochete bacteria B. burgdorferi.