Persistence of Brucella abortus in the livers of T cell-deficient nude mice.

BACKGROUND: Brucella abortus is sequestered in lymphoid tissues, bone, and liver during chronic asymptomatic brucellosis of cattle and humans. The sites of cellular infection, cytopathology of infected cells, and mechanisms of bacterial recrudescence have not been identified. A laboratory model is needed for the study of chronic brucellosis. EXPERIMENTAL
DESIGN: Livers of athymic and euthymic mice infected with virulent B. abortus were cultured and examined morphologically to determine the effects of T cell dysfunction on persistence of intracellular bacteria. Bacterial Ag was detected immunohistochemically and by ultrastructural immunogold techniques.
RESULTS: Bacteria in livers of euthymic mice rose to high titers at postinoculation Day (PID) 6 but rapidly declined and were slowly cleared. In athymic mice, bacteria did not reach such high titers and persisted in all mice to PID 121. Granulomas were similar in size, structure, and number in both groups of mice through PID 28. Thereafter, euthymic mice developed many granulomas that disappeared by PID 121. In contrast, athymic mice failed to maintain granuloma formation but had diffuse lymphohistiocytic pericholangiitis with brucella Ag in subepithelial stellate cells, intraepithelial monocytes, and luminal macrophages. Intact bacteria were identified in lysosomes of macrophages and neutrophils only in acute infection.
CONCLUSIONS: Athymic mice have normal or enhanced resistance to B. abortus in the first 10 days of infection but fail to maintain granuloma formation, do not clear brucellae from the liver, and develop persistent infection of the biliary tract. Brucellar Ag persists in chronically infected livers in periductal inflammatory tissues.