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Updated: Aug 24, 2026
Depletion and Reconstitution of Macrophages in Mice
Published on: August 1, 2012
Role of macrophages in a mouse model of postoperative MRSA enteritis
Hidenori Tanaka1, Shuichi Miyazaki, Yoshinobu Sumiyama
1Department of Microbiology, Toho University School of Medicine, 5-21-16 Omori-nishi, Ota-ku, Tokyo 143-8540, Japan.
Background:
We have established a mouse model for fatal postoperative enteritis due to Staphylococcus aureus to analyze mechanisms of bacterial translocation and determine reasons for the lethality of this infection. In the present study the role of macrophages was ascertained in protection against S. aureus induced enteritis.
Materials And Methods:
Mice were pretreated with cyclophosphamide (CY), an immunosuppressant, and then infected directly into the jejunum with methicillin-resistant S. aureus (MRSA) isolated from a patient. In other groups of mice liposome-encapsulated dichloromethylene diphosphate (Cl2MDP) was administered to deplete macrophages in vivo. Other experimental groups received lipoteichoic acid (LTA), which was used to inhibit the ability of macrophages to bind MRSA, and additionally, to analyze dependence of bacterial clearance on the macrophage scavenger receptor. The ability of macrophages to bind MRSA was compared with survival rates in this mouse model of fatal postoperative enteritis.
Results:
Injection of liposome-encapsulated Cl2MDP decreased survival rate of mice infected intraintestinally with MRSA in a dose-dependent manner. Cyclophosphamide also decreased survival rate of MRSA-infected mice and was found to correlate with its ability to decrease the number of macrophages in the spleen. Intravenous LTA administration did not affect total splenocyte numbers or the number of splenic macrophages but decreased the ability of macrophages to bind MRSA and adversely affected survival of mice infected with MRSA.
Conclusions:
Macrophages play a critical role in protection against MRSA administered directly into the jejunum. LTA recognition sites (probably type A scavenger receptors) on macrophages are required for binding and phagocytosing MRSA.
Insights
Macrophages are crucial for preventing fatal Staphylococcus aureus enteritis in mice. Their ability to bind MRSA, mediated by lipoteichoic acid recognition sites, is essential for survival.
Area of Science:
- Immunology
- Microbiology
- Gastroenterology
Background:
- Established a mouse model for fatal postoperative enteritis caused by Staphylococcus aureus.
- Investigated mechanisms of bacterial translocation and lethality in S. aureus infections.
- Focused on the protective role of macrophages against S. aureus-induced enteritis.
Purpose of the Study:
- To ascertain the role of macrophages in protection against S. aureus-induced enteritis.
- To analyze the dependence of bacterial clearance on macrophage scavenger receptors.
- To compare macrophage binding ability with survival rates in a fatal enteritis model.
Main Methods:
- Used a mouse model with jejunal infection of methicillin-resistant S. aureus (MRSA).
- Administered cyclophosphamide (CY) to suppress immune function.
- Depleted macrophages using liposome-encapsulated dichloromethylene diphosphate (Cl2MDP).
- Inhibited macrophage-MRSA binding with lipoteichoic acid (LTA).
Main Results:
- Macrophage depletion (Cl2MDP) and immunosuppression (CY) significantly decreased survival rates in MRSA-infected mice.
- Lipoteichoic acid (LTA) administration impaired macrophage binding of MRSA and reduced survival.
- Reduced macrophage numbers correlated with decreased survival following CY treatment.
Conclusions:
- Macrophages are critical for host defense against jejunal MRSA infection.
- Lipoteichoic acid recognition sites on macrophages are essential for binding and phagocytosing MRSA.
- Macrophage scavenger receptors are implicated in MRSA clearance.
