Spatiotemporal dynamics of multi-organ pathology and antigen localization in BALB/c mice following intragastric infection with

Brucellosis is a globally distributed zoonosis that invades hosts mainly through the gastrointestinal route, yet the spatiotemporal patterns of organ colonization and tissue injury following intragastric Brucella infection remain poorly defined. Objective: To investigate the dynamic colonization patterns, histopathological progression, and spatiotemporal antigen localization characteristics of Methods: The mice were randomly divided into an uninfected control group and infection groups euthanized at 1, 3, 7, 14, 28, 42, and 56 days post-infection (dpi). Mice received intragastric inoculation of 10 Results: After intragastric infection, mice developed prominent splenomegaly and transient hepatic weight gain, both peaking at 14 dpi in the acute phase. Splenic bacterial load reached its maximum at 14 dpi, then declined gradually but remained at relatively high levels throughout the chronic phase until 56 dpi. The liver was rapidly colonized in the early stage; hepatic bacterial load rose in the acute phase and decreased markedly in the late chronic stage. Transient infection was observed in the lungs and MLNs. Renal tissue maintained intact histological architecture with consistently negative IHC signals across all time points. Multiple hepatic granulomas were detected, with most IHC-positive antigens confined within granulomatous lesions. In the spleen, severe marginal zone histiocytic infiltration occurred in the acute phase, while an imbalanced red-to-white pulp ratio and abundant megakaryocytes emerged in the chronic phase, with bacterial antigens persistently localized in organized histiocytes. Flow cytometry showed splenic DC proportion peaked at 2 weeks, whereas hepatic DCs increased moderately and plateaued between 2 and 4 weeks. Conclusions: This study characterizes distinct organ-specific colonization phenotypes, pathological progression, and DC alterations of