title: Role of macrophages in a mouse model of postoperative MRSA enteritis.
abstract: 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.
  
  
  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.
authors.affiliation: Department of Microbiology, Toho University School of Medicine, 5-21-16 Omori-nishi, Ota-ku, Tokyo 143-8540, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Tanaka
authors.forename: Shuichi
authors.initials: S
authors.lastname: Miyazaki
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Sumiyama
authors.forename: Terutaka
authors.initials: T
authors.lastname: Kakiuchi
mesh_terms: D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D004002:Clodronic Acid / Q000494:pharmacology; D003520:Cyclophosphamide / Q000494:pharmacology; D004195:Disease Models, Animal; D004751:Enteritis / Q000188:drug therapy / Q000276:immunology* / Q000382:microbiology; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000276:immunology* / Q000382:microbiology; D008297:Male; D016106:Methicillin Resistance; D051379:Mice; D008807:Mice, Inbred BALB C; D010587:Phagocytosis / Q000276:immunology; D011183:Postoperative Complications / Q000188:drug therapy / Q000276:immunology / Q000382:microbiology; D013047:Specific Pathogen-Free Organisms; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000276:immunology*; D013682:Teichoic Acids / Q000494:pharmacology
chemical_list: D000963:Antimetabolites; D007166:Immunosuppressive Agents; D008070:Lipopolysaccharides; D013682:Teichoic Acids; D004002:Clodronic Acid; C009900:lipoteichoic acid; D003520:Cyclophosphamide