lipoteichoic-acid and Enteritis

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.. 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.. 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.. 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.

Topics: Animals; Antimetabolites; Clodronic Acid; Cyclophosphamide; Disease Models, Animal; Enteritis; Immunosuppressive Agents; Lipopolysaccharides; Macrophages, Peritoneal; Male; Methicillin Resistance; Mice; Mice, Inbred BALB C; Phagocytosis; Postoperative Complications; Specific Pathogen-Free Organisms; Staphylococcal Infections; Teichoic Acids