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 human s. The sites of cellular infection, cytopathology of infected cells, a nd mechanisms of bacterial recrudescence have not been identified. A l aboratory model is needed for the study of chronic brucellosis. EXPERI MENTAL DESIGN: Livers of athymic and euthymic mice infected with virul ent B. abortus were cultured and examined morphologically to determine the effects of T cell dysfunction on persistence of intracellular bac teria. Bacterial Ag was detected immunohistochemically and by ultrastr uctural immunogold techniques. RESULTS: Bacteria in livers of euthymic mice rose to high titers at postinoculation Day (PID) 6 but rapidly d eclined and were slowly cleared. In athymic mice, bacteria did not rea ch such high titers and persisted in all mice to PID 121. Granulomas w ere similar in size, structure, and number in both groups of mice thro ugh PID 28. Thereafter, euthymic mice developed many granulomas that d isappeared by PID 121. In contrast, athymic mice faded to maintain gra nuloma formation but had diffuse lymphohistiocytic pericholangitis wit h brucella Ag in subepithelial stellate cells, intraepithelial monocyt es, and luminal macrophages. Intact bacteria were identified in lysoso mes of macrophages and neutrophils only in acute infection. CONCLUSION S: Athymic mice have normal or enhanced resistance to B. abortus in th e first 10 days of infection but fail to maintain granuloma formation, do not clear brucellae from the liver, and develop persistent infecti on of the biliary tract. Brucellar Ag persists in chronically infected livers in periductal inflammatory tissues.