Abstract
Brucella abortus injected into CBA mice replicated primarily in the spleen and liver, reaching a peak bacterial count in both organs about 7 days postinfection. The organism was eliminated from the liver but declined to a chronic phase in the spleen. The infection caused hepatosplenomegaly. An influx of macrophages into the two organs was monitored by quantitative Northern (RNA blot) analysis of the macrophage-specific marker lysozyme mRNA. Lysozyme mRNA was detectable in spleen and increased three- to fourfold during infection. In liver, lysozyme mRNA was initially undetectable, but at about the peak of infection it reached a level comparable to that in the spleen. Macrophage colony-stimulating factor 1 (CSF-1) has been reported to be elevated in the circulation of animals infected with B. abortus and is known to stimulate monocytopoiesis. To investigate the role of CSF-1 in pathogenesis, we studied the effect of further increasing the CSF-1 concentration by administration of recombinant human CSF-1. Since the infection is characterized by several distinct phases, recombinant human CSF-1 was administered at defined times relative to these phases. Pronounced effects were observed only when CSF-1 administration was begun during the developing acute phase. The consequences were decreased bacterial numbers in the spleen but an increase in the liver, reduced antibody generation, and increased hepatosplenomegaly. A feature of many chronic intracellular infections is immunosuppression. B. abortus caused a substantial diminution of responsiveness of spleen cells to T-cell mitogens, particularly concanavalin A. This action was mimicked by CSF-1 treatment of the animals prior to spleen cell isolation. The results suggest that CSF-1 plays a role in macrophage recruitment in brucellosis and that recruited macrophages contribute to the immunopathology and immunosuppression.
Original language | English |
---|---|
Pages (from-to) | 1465-72 |
Number of pages | 8 |
Journal | Infection and Immunity |
Volume | 60 |
Issue number | 4 |
Publication status | Published - Apr 1992 |
Keywords / Materials (for Non-textual outputs)
- Animals
- Antibody Formation
- Blotting, Northern
- Brucellosis
- Colony-Forming Units Assay
- Disease Models, Animal
- Dose-Response Relationship, Immunologic
- Hepatomegaly
- Hypersensitivity, Delayed
- Liver
- Lung
- Lymphocyte Activation
- Macrophage Colony-Stimulating Factor
- Macrophages
- Mice
- Mice, Inbred CBA
- Muramidase
- Organ Size
- RNA, Messenger
- Recombinant Proteins
- Spleen
- Splenomegaly
- Time Factors