8^th European Immunology Conference

Biography

Biography: Eva M Carmona

Abstract

The NLRP3 inflammasome is activated in response to different bacterial, viral and fungal pathogens and serves as modulator of different pattern recognition receptor signalling pathways. Herein, we have investigated the role of NLRP3 in human circulating B-lymphocytes and identify that it is essential for two independent processes, pro-inflammatory cytokine and antibody regulation. Our results show that β-glucan stimulated B lymphocytes secrete IL-1β, which is important in the host defence against Pneumocystis and other fungal infections. IL-1β maturation and secretion by circulating B-lymphocytes is regulated by the NLRP3 inflammasome, which was dependent on ATP and potassium (K+) efflux. The inhibition of NLRP3 and CASP1 by specific inhibitors abolished the secretion of IL-1β. β-glucan mediated IL-1β secretion was partially mediated by Dectin-1 activation via SYK and the transcription factors NF-κB and AP-1. Furthermore, we demonstrated that B-lymphocytes activated by unmethylated CpG motifs, found in bacterial DNA, induced the production and secretion of IgM antibodies. Interestingly, this process also requires the activation of the NLRP3 inflammasome. Similar to IL-1β, B-lymphocyte stimulation by CpG resulted in NLRP3 and CASP1 activation. IgM production was inhibited by specific CASP1 and NLRP3 inhibitors and was dependent on ATP and potassium (K+) efflux. Furthermore, we identified that CPG-stimulated IgM secretion unlike IL-1β was mTOR-mediated. In conclusion, this study identifies the NLRP3 inflammasome as modulator of the innate and adaptive immune systems in response to fungal and bacterial stimuli in human circulating B-lymphocytes.