title: Course of infection with the emergent pathogen Brucella microti in immunocompromised mice.
abstract: A new Brucella species, Brucella microti, has been isolated from wild rodents and found to be pathogenic in mice. The biological relevance of this new mouse pathogen is clear, as it allows us to study Brucella infection in a species-specific model. The course of infection in wild-type (wt) and immunodeficient mice that lack B (Jh), T and B (SCID), or T, B, and NK (SCID.Beige) cells was analyzed over 3 weeks. wt mice completely cleared bacteria from the liver and spleen after that time. However, SCID mice showed a much higher bacterial load in the spleen and liver than wt and Jh mice after 1 week and maintained the same level during the next 2 weeks. All mice tested survived for the 3 weeks. In contrast, the bacterial levels in mice that lacked NK cell activity progressively increased and these mice succumbed to infection after 16 to 18 days. Histopathology analysis of infected mice showed extensive areas of necrotic tissue and thrombosis in liver after 1 week in all infected SCID.Beige mice but were not seen in either SCID or wt animals. These processes were dramatically increased after 21 days, corresponding with the death of SCID.Beige animals. Our results indicate that T and/or B cells are required for the control of infection with the mouse pathogen Brucella microti in liver and spleen but that NK cells are crucial for survival in the absence of B and T cells. In addition, they suggest that controlled granuloma formation is critical to clear this type of infection in wt mice.
authors.affiliation: Unidad de Sanidad Animal, Centro de Investigación y Tecnología, Gobierno de Aragón, Zaragoza, Spain. mpjimenezdebagues@aragon.es
authors.forename: María P
authors.initials: MP
authors.lastname: Jiménez de Bagüés
authors.forename: Alba
authors.initials: A
authors.lastname: de Martino
authors.forename: Juan F
authors.initials: JF
authors.lastname: Quintana
authors.forename: Ana
authors.initials: A
authors.lastname: Alcaraz
authors.forename: Julián
authors.initials: J
authors.lastname: Pardo
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D058491:Bacterial Load; D002002:Brucella / Q000145:classification / Q000276:immunology / Q000472:pathogenicity*; D002006:Brucellosis / Q000276:immunology* / Q000382:microbiology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D016867:Immunocompromised Host; D007694:Killer Cells, Natural / Q000276:immunology; D008099:Liver / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D013045:Species Specificity; D013154:Spleen / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology