Oral Brucella melitensis infection leads to persistent bacterial colonisation and dynamic histopathology in reproductive and immune organs of female mice.

Oral infection is a major route of Brucella transmission; however, systematic reports on the dynamic multiorgan damage induced by this route are still lacking. Brucella preferentially colonises reproductive organs (e.g., the uterus) and immune organs, leading to reproductive system diseases and chronic infection in humans. In this study, female BALB/c mice were inoculated with Brucella melitensis (B. melitensis) via intragastric gavage. Uterus, spleen, lung, and lymph node samples were collected over 8 weeks post-infection, and bacterial burden, organ weight, H&E histopathology, immunohistochemical staining for Brucella antigen, and flow cytometric analysis of F4/80+CD11b+ macrophages were evaluated. The results showed that bacteria were detectable in all examined organs as early as 1 day post-infection, indicating rapid dissemination from the gastrointestinal tract. Bacterial loads in the lung and lymph nodes peaked at 1 week and then declined, but remained detectable up to 8 weeks. In the spleen and uterus, bacterial loads peaked at 2 weeks, and the bacterial load in the reproductive organ (uterus) was consistently lower than that in immune organs (spleen and lymph nodes). Splenic weight peaked at 2 weeks, whereas uterine weight peaked at 4 weeks. Histopathology revealed that the most severe lesions in the uterus, spleen, and lymph nodes occurred at 2 weeks post-infection, with bacteria persisting up to 8 weeks. The lung exhibited acute lesions followed by marked inflammatory resolution, with a significant reduction in bacterial load at 8 weeks. Flow cytometry showed that the proportion of F4/80+CD11b+ macrophages in the uterus and spleen increased significantly from 1 to 4 weeks post-infection, peaked at 2 weeks, and gradually decreased to levels below those of the PBS control group by 8 weeks (p<0.01). This study systematically describes the dynamic pathological and immunological changes in the reproductive and immune organs of mice following oral Brucella infection, providing a mouse model basis for studies on the pathogenesis of brucellosis and vaccine evaluation.