title: Staphylococcal superantigens cause lethal pulmonary disease in rabbits.
abstract: BACKGROUND
  The Centers for Disease Control and Prevention (CDC) and others reported that methicillin-resistant S. aureus (MRSA) are significant causes of serious human infections, including pulmonary illnesses. We investigated the role played by superantigens in lung-associated lethal illness in rabbits.
  
  
  METHODS
  A rabbit model was established to investigate the potential role played by superantigens, staphylococcal enterotoxin B (SEB), staphylococcal enterotoxin C (SEC), and toxic shock syndrome toxin-1 (TSST-1). Rabbits received intrabronchial community-associated (CA) MRSA strains USA200 (TSST-1(+)), MW2 (SEC(+)), c99-529 (SEB(+)), or purified superantigens. Some rabbits were preimmunized against superantigens or treated with soluble high-affinity T cell receptors (Vβ-TCR) to neutralize SEB and then challenged intrabronchially with CA-MRSA or superantigens.
  
  
  RESULTS
  Rabbits challenged with CA-MRSA or superantigens developed fatal, pulmonary illnesses. Animals preimmunized against purified superantigens, or treated passively with Vβ-TCRs and then challenged with CA-MRSA or superantigens, survived. Lung histological analysis indicated that nonimmune animals developed lesions consistent with necrotizing pneumonia after challenge with CA-MRSA or purified superantigens. Superantigen-immune animals or animals treated with soluble Vβ-TCRs did not develop pulmonary lesions.
  
  
  CONCLUSIONS
  Superantigens contribute to lethal pulmonary illnesses due to CA-MRSA; preexisting immunity to superantigens prevents lethality. Administration of high-affinity Vβ-TCR with specificity for SEB to nonimmune animals protects from lethal pulmonary illness resulting from SEB(+) CA-MRSA and SEB.
authors.affiliation: Department of Microbiology, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA. stran094@umn.edu
authors.forename: Kristi L
authors.initials: KL
authors.lastname: Strandberg
authors.forename: Jessica H
authors.initials: JH
authors.lastname: Rotschafer
authors.forename: Sara M
authors.initials: SM
authors.lastname: Vetter
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Buonpane
authors.forename: David M
authors.initials: DM
authors.lastname: Kranz
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Schlievert
mesh_terms: D000818:Animals; D001427:Bacterial Toxins / Q000008:administration & dosage / Q000276:immunology; D004195:Disease Models, Animal; D004768:Enterotoxins / Q000008:administration & dosage / Q000276:immunology; D008171:Lung Diseases / Q000276:immunology* / Q000382:microbiology / Q000401:mortality / Q000473:pathology; D055624:Methicillin-Resistant Staphylococcus aureus / Q000276:immunology; D011817:Rabbits; D013203:Staphylococcal Infections / Q000276:immunology* / Q000382:microbiology / Q000401:mortality / Q000473:pathology; D013211:Staphylococcus aureus / Q000276:immunology*; D018089:Superantigens / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D001427:Bacterial Toxins; D004768:Enterotoxins; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal; C031818:enterotoxin B, staphylococcal; C034959:enterotoxin C, staphylococcal