A new murine model of Brucella-induced spondyloarthritis
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| Autores: | , , , |
|---|---|
| Format: | artículo original |
| Status: | Versión publicada |
| Fecha de Publicación: | 2026 |
| Beskrivelse: | Osteoarticular disease, including large joint arthritis, sacroiliitis and spondylitis, repre- sents the most common complication of chronic brucellosis in humans. Study of chronic manifestations has been hampered by the lack of a tractable mouse model. To this end, we infected spondyloarthritis-susceptible “SKG” mice bearing a mutation in the TCR- associated signaling adaptor ZAP70. Infection with B. melitensis resulted in late onset (4 weeks) arthritis followed by peri-orbital eye inflammation and finally scaly skin rash in a smaller subset. Arthritis was 100% penetrant and easily scored. Colony forming units were detected in spleen and infected paw synovium 11-12 weeks post-infection, suggesting active persistent infection. In contrast, injection of heat-killed B. melitensis resulted in only mild eye inflammation and failure to gain weight, but no arthritis or rash. Infection with B.neotomae, a rare human pathogen, resulted in notably milder disease, revealed sex differences (milder in males), and arthritis dose responses in females. We used in vivo imaging (IVIS) to track luminescent B. neotomae infection, as BSL3 IVIS was not available. Paw luminescence peaked at 1 week, and then gradually abated, but persisted to 12 weeks. However, average onset of clinical arthritis was 46.5 weeks and thus did not strictly correlate with luminescence. To begin evaluating requirements for bacterial virulence factors, we used several Brucella mutants: Delta VirB Brucella induced eye inflammation similar to wild type, but less penetrant (45%), delayed and very mild arthritis. Brucella lacking the secreted virulence factor VceC are deficient in UPR induction. Preliminary data in our model suggests deficient CHOP and IL23 induction and minimal transient arthritis induction. In summary, we have developed a murine model for chronic Brucella-induced arthritis that is highly penetrant, easily scored, and displays sufficient dynamic range to enable comparisons of different Brucella species and mutants. This model will provide new insights into disease pathogenesis. |
| País: | Portal de Revistas UNA |
| Institution: | Universidad Nacional de Costa Rica |
| Repositorio: | Portal de Revistas UNA |
| Sprog: | Inglés |
| OAI Identifier: | oai:www.revistas.una.ac.cr:article/23037 |
| Online adgang: | https://www.revistas.una.ac.cr/index.php/veterinaria/article/view/23037 |
| Palabra clave: | Animal model Brucella Murines spondyloarthritis Brucella melitensis |