Staphylococcus aureus enterotoxin G (SEG) induces in vitro resistance to glucocorticoid treatment

FERNANDEZ LYNCH MJ; NOLI TRUANT S; ANTONOGLOU B; TODONE M; ROMASANTA P; SARRATEA B; DE MARZI MC; MALCHIODI EL; FERNANDEZ M

Mar del Plata, Buenos Aires

Congreso; LIX Reunión Científica Anual, SAIC, LXII Reunión Anual SAI; 2014

Sociedad Argentina de Inmunología-Sociedad Argentina de Investigación Clínica

Ver adjunto pagina 191 Bacterial superantigens (SAgs) are bacterial proteins which bind in a non-classical way to TCR-MHC-II complexes inducing a peptide-non-specific proliferation of T lymphocytes. Staphylococcus aureus produces a wide range of enterotoxins, including type II SAg SEG. SAg related diseases are commonly treated with a combination of: antibiotics, if the bacteria are present; systemic glucocorticoids, for modulating the exacerbated response; and hemodynamic support for severe cases. Recently, resistance to the glucocorticoid traditional treatment was described for SEB, another type II SAg. In order to elucidate whether glucocorticoid resistance is extended to other members of the type II family, mouse splenocytes were treated with 1 and 10 μg/ml of SEG, showing significant proliferation at high doses of dexamethasone (10-5 M); SEG 1μg/ml: (2208 ± 15) cpm; SEG 10μg/ml: (3017 ± 59) cpm compared to control (161 ± 75) cpm; whereas classical LT-mythogen PHA proliferation is inhibited at low glucocorticoid doses (10-8M). The addition of 0.0025 and 0.025 μg/ml of S. aureus peptidoglycan enhances the resistance at higher dexamethasone doses. Moreover, SEG site directed mutants D172A, F204A, G20A, N24A and N24D, which involve TCR ?hot spots? binding residues, show decreased in vitro activity and glucorticoid inhibition at lower doses. These results suggest that the activation of TCR signaling might be necessary for glucocorticoid resistance. The understanding of the underlying mechanisms of superantigen glucorticoid resistance might lead to more effective treatments of the pathologies related to these toxins.