Staphylococcal Superantigens Cause Lethal Pulmonary Disease in Rabbits

Background. The Centers for Disease Control and Prevention (CDC) and others reported that methicillinresistant 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 , and toxic chock 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 CAMRSA or superantigens, survived. Lung histological analysis indicated that nonimmune animals developed lesions consistent with necrotizing pneumonia after challenge with CA-MRSA or purified superantigens. Superantigenimmune animals or animals treated with soluble Vb-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.