Shedding of IL-1 receptor type II (IL-1RII) as a regulatory mechanism for interleukin 1 (IL-1) βeta availability during Staphylococcus aureus infection

GAI, CONSTANZA; GONZALEZ, CINTIA; GARÓFALO, AILÍN; SABBIONE, FLORENCIA; BIANI, CELESTE; TREVANI, ANALIA; GÓMEZ, MARISA

Buenos Aires

Congreso; Congreso Internacional SAI-FAIC; 2015

Sociedad Franco Argentina de Inmunología

Abstract: IL-1β is a critical cytokine that orchestrates effective host defenses against S. aureus. IL-1RII acts as a decoy receptor regulating the biological effects of IL-1β. High levels of soluble IL-1RII are present in septic patients; however, the stimuli that regulate its expression and release during infection are not completely understood. The aim of this study was to determine the ability of S. aureus to induce IL-1RII shedding in myeloid cells and the consequences of this process during systemic infection. Human monocytes and neutrophils purified from peripheral blood expressed IL-1RII on the surface. Upon S. aureus stimulation, a significant increase in the release of soluble IL-1RII was observed. In monocytes, this process was dependent on protein A expression as evidenced using a SpA- mutant. In vivo studies using a model of systemic infection allowed demonstrate that S. aureus induces the transcription of IL-1RI, IL-1Ra and IL-1RII at 2 hours post-challenge in peritoneal cells. Conversely, the spa- mutant did not induce an increase in IL-1Ra and IL-1RII expression. The levels of IL-1β in serum and in peritoneal infiltrates, were significantly increased in response to the spa- mutant whereas no IL-1β was detected in mice challenged with S. aureus. In addition, the percentage of neutrophils recruited to the peritoneum 24 hours after inoculation was significantly lower in mice challenged with S. aureus than in the spa- group. In conclusion, the positive modulation of IL-1RII expression and cleavage induced