Effect of recombinant human macrophage colony-stimulating factor 1 on immunopathology of experimental brucellosis in mice

A G Doyle, W J Halliday, C J Barnett, T L Dunn, D A Hume

Research output: Contribution to journalArticlepeer-review

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 languageEnglish
Pages (from-to)1465-72
Number of pages8
JournalInfection and Immunity
Volume60
Issue number4
Publication statusPublished - 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

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