Staphylococcus aureus egc and group II superantigens induce glucocorticoid resistance in human peripheral blood mononuclear cells(PBMCs).

FERNÁNDEZ LYNCH MARÍA JULIETA; NOLI TRUANT, SOFIA; ANTONOGLOU, BELÉN; TODONE MARCOS; ROMASANTA, PABLO N.; SARRATEA, BELÉN; DE MARZI MAURICIO; MALCHIODI EMILIO LUIS; FERNÁNDEZ MARISA MARIEL

Ciudad Autónoma de Buenos Aires

Congreso; I Meeting LASID/FAIC/SAI, LXIII REUNIÓN CIENTÍFICA DE LA SOCIEDAD ARGENTINA DE INMUNOLOGÍA.; 2015

SOCIEDAD ARGENTINA DE INMUNOLOGÍA. SAI

Background: Superantigens are exotoxins that bind in a non-classical way to T-cell receptor (TCR) and Mayor Histocompatibility Complex triggering peptide-non-specific T cell proliferation and proinflammatory cytokine release. Immunosupressant such as glucocorticoids, are used to revertinflammatory actions in Staphylococcus aureus toxin related diseases. However, resistance to treatment has been reported for SEB and TSST-1 [HAUK 2000]. Here, we aim to elucidate whether the enterotoxin gene cluster toxins SEG, SEI and SEO, and other group II toxins (SEC3, SER and SSA) can induce resistance to dexamethasone in human PBMCs.Methods: Recombinant superantigens SEG, SEI, SEO, SEC3, SER, SSA and SEG mutants with low affinity for TCR: D172A, G20A, F204A, N24A and N24D were produced in E. coli BL21 and purifiedby Ni-NTA. Purified PBMCs were cultured for 48/72 hours for proliferation assessment with 3H-thymidine under different stimuli: 1-10 μg/ml superantigens, 10-9-10-5 M dexamethasone and 1-10 μM PI3K inhibitor Ly294002.Results: PBMCs treated with 1 μg/ml of SEC3 or SEI and 10 μg/ml of SEG, SER, SEO or SSA showed significant proliferation at high doses of dexamethasone (10-5 M) comparing with control cells (p