The impact of Staphylococcus aureus-associated molecular patterns on staphylococcal superantigen-induced toxic shock syndrome and pneumonia.

Staphylococcus aureus is capable of causing a spectrum of human illnesses. During serious S. aureus infections, the staphylococcal pathogen-associated molecular patterns (PAMPs) such as peptidoglycan, lipoteichoic acid, and lipoproteins and even intact S. aureus, are believed to act in conjunction with the staphylococcal superantigens (SSAg) to activate the innate and adaptive immune system, respectively, and cause immunopathology. However, recent studies have shown that staphylococcal PAMPs could suppress inflammation by several mechanisms and protect from staphylococcal toxic shock syndrome, a life-threatening systemic disease caused by toxigenic S. aureus. Given the contradictory pro- and anti-inflammatory roles of staphylococcal PAMPs, we examined the effects of S. aureus-derived molecular patterns on immune responses driven by SSAg in vivo using HLA-DR3 and HLA-DQ8 transgenic mice. Our study showed that neither S. aureus-derived peptidoglycans (PGN), lipoteichoic acid (LTA), nor heat-killed Staphylococcus aureus (HKSA) inhibited SSAg-induced T cell proliferation in vitro. They failed to antagonize the immunostimulatory effects of SSAg in vivo as determined by their inability to attenuate systemic cytokine/chemokine response and reduce SSAg-induced T cell expansion. These staphylococcal PAMPs also failed to protect HLA-DR3 as well as HLA-DQ8 transgenic mice from either SSAg-induced toxic shock or pneumonia induced by a SSAg-producing strain of S. aureus.

Superantigen profiling of Staphylococcus aureus infective endocarditis isolates.

The frequency of superantigen production among Staphylococcus aureus isolates associated with endocarditis is not well defined. We tested 154 S. aureus isolates from definite infective endocarditis cases for the presence of staphylococcal enterotoxins A-E, H, and TSST-1 by PCR, enzyme-linked immunosorbent assay, and using an HLA-DR3 transgenic mouse splenocyte proliferation assay. Sixty-three isolates (50.8%) tested positive for at least 1 superantigen gene, with 21 (16.9%) testing positive for more than 2. tst (28.6%) was most common, followed by seb (27%), sea (22.2%), sed (20.6%), see (17.5%), and sec (11.1%). Of 41 methicillin-resistant S. aureus, 21 had superantigen genes, with sed being more frequently detected in this group compared to methicillin-susceptible S. aureus (P < 0.05). Superantigen genes were not associated with mortality (P = 0.81). 75% of PCR-positive isolates induced robust splenocyte proliferation. Overall, more than half of S. aureus isolates causing endocarditis carry superantigen genes, of which most are functional.