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Primary listerial infections are exacerbated in mice administered neutralizing antibody to macrophage
S H Gregory1, E J Wing, D J Tweardy
1Department of Medicine, University of Pittsburgh School of Medicine, PA 15213.
Abstract:
The serum and tissue levels of macrophage colony-stimulating factor (M-CSF) are elevated in mice during a primary immunologic response to infection by Listeria monocytogenes. Experiments were performed to determine the specific role of M-CSF in the resolution of listerial infections. The bulk of Listeria injected into a mouse i.v. is deposited in the liver. The expression of M-CSF mRNA in the liver increased markedly within 2 h postinfection. Maximum expression was dependent upon the dose of Listeria inoculated. The administration of anti-M-CSF mAb reduced the percentage of Mac-1+ mononuclear phagocytes subsequently found in the livers of infected animals. This reduction correlated inversely with an increase in the number of Listeria associated with both the parenchymal and NPC populations. These results suggest that M-CSF may play an important role in the primary immunologic response to Listeria in the liver by stimulating the production, mobilization, and/or biologic activity of Mac-1+ mononuclear phagocytes.
Insights
Macrophage colony-stimulating factor (M-CSF) aids the immune response against Listeria monocytogenes infection. Blocking M-CSF reduces key immune cells in the liver, increasing bacterial load.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Macrophage colony-stimulating factor (M-CSF) levels rise during Listeria monocytogenes infection.
- M-CSF is crucial for mononuclear phagocyte development and function.
Purpose of the Study:
- To investigate the specific role of M-CSF in resolving Listeria infections.
- To understand M-CSF's impact on immune cell populations in the liver.
Main Methods:
- Mice were infected intravenously with Listeria monocytogenes.
- M-CSF mRNA expression in the liver was quantified post-infection.
- Anti-M-CSF monoclonal antibodies (mAbs) were administered to block M-CSF activity.
- Mononuclear phagocyte populations (Mac-1+) and Listeria burden in the liver were assessed.
Main Results:
- M-CSF mRNA expression in the liver increased rapidly after Listeria infection, dose-dependently.
- Blocking M-CSF with mAbs decreased Mac-1+ mononuclear phagocytes in the liver.
- Reduced M-CSF activity correlated with increased Listeria loads in both parenchymal and non-parenchymal liver cells.
Conclusions:
- M-CSF plays a significant role in the primary immune response to Listeria in the liver.
- M-CSF appears to stimulate the production, mobilization, and/or activity of Mac-1+ mononuclear phagocytes during infection.