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.