Impaired control of Brucella melitensis infection in Rag1-deficient mice

After intranasal inoculation, Brucella melitensis chronically infects the m ononuclear phagocyte system in BALB/c mice, but it causes no apparent illne ss. Adaptive immunity. which can be transferred by either T cells or antibo dy from immune to naive animals, confers resistance to challenge infection. The role of innate, non-B-, non-T-cell-mediated immunity in control of mur ine brucellosis, however, is unknown. In the present study, we documented t hat BALB/c and C57BL/6 mice had a similar course of infection after intrana sal administration of 16M, validating the usefulness of the model in the la tter mouse strain. me then compared the course of infection in Rag1 knockou t mice (C57BL/6 background) (referred to here as RAG-1 mice) which have no B or T cells as a consequence of deletion of Rag1 (recombination-activating gene 1), with infection in normal C57BL/6 animals after intranasal adminis tration of B. melitensis 16M. C57BL/6 mice cleared brucellae from their lun gs by 8 to 12 weeks and controlled infection in the liver and spleen at a l ow level. In contrast, RAG-1 mice failed to reduce the number of bacteria i n any of these organs. From 1 to 4 weeks after inoculation, the number of s plenic bacteria increased from 2 to 4.5 logs and remained at that level. In contrast to the consistently high numbers of brucellae observed in the spl eens, the number of bacteria rose in the livers sampled for up to 20 weeks. Immunohistologic examination at 8 weeks after infection disclosed foci of persistent pneumonia and large amounts of Brucella antigen in macrophages i n lung, liver, and spleen in RAG-1, but not C57BL/6, mice. These studies in dicate that T- and B-cell-independent immunity can control Brucella infecti on at a high level in the murine spleen, but not in the liver. Immunity med iated by T and/or B cells is required for clearance of bacteria from spleen and lung and for control of bacterial replication in the liver.