RNA and beta-Hemolysin of Group B Streptococcus Induce Interleukin-1 beta ( IL-1 beta) by Activating NLRP3 Inflammasomes in Mouse Macrophages

Rahul Gupta (1) , Shubhendu Ghosh (1) , Brian Monks (1) , Rosane B. Deoliveira (1) , Te-Chen Tzeng (1) , Parisa Kalantari (1) , Anubhab Nandy (1) , Bornali Bhattacharjee (1) , Jennie Chan (1) , Fabianno Ferreira (2) , Vijay Rathinam (1) , Shruti Sharma (1) , Egil Lien (1) , Neal Silverman (1) , Katherine Fitzgerald (1) , Arnaud Firon (3) , Patrick Trieu-Cuot (3) , Philipp Henneke (4) , Douglas T. Golenbock (1)

1 Division of Infectious Diseases and Immunology
2 Laboratório de Inflamação e Imunidade
3 Biologie des Bactéries pathogènes à Gram-positif
4 Center for Chronic Immunodeficiency (CCI), University Medical Center Freiburg, Freiburg, Germany

The inflammatory cytokine IL-1β is critical for host responses against many human pathogens. Here, we define Group B Streptococcus (GBS)-mediated activation of the Nod-like receptor-P3 (NLRP3) inflammasome in macrophages. NLRP3 activation requires GBS expression of the cytolytic toxin, β-hemolysin, lysosomal acidification, and leakage. These processes allow the interaction of GBS RNA with cytosolic NLRP3. The present study supports a model in which GBS RNA, along with lysosomal components including cathepsins, leaks out of lysosomes and interacts with NLRP3 to induce IL-1β production.

Keywords: Cell Signaling; Immunology; Innate Immunity; Interleukin; RNA

Domains: Life Sciences [q-bio]; Microbiology and Parasitology; Bacteriology

Rahul Gupta, Shubhendu Ghosh, Brian Monks, Rosane B. Deoliveira, Te-Chen Tzeng, et al.. RNA and beta-Hemolysin of Group B Streptococcus Induce Interleukin-1 beta ( IL-1 beta) by Activating NLRP3 Inflammasomes in Mouse Macrophages. Journal of Biological Chemistry, 2014, 289 (20), pp.13701-13705. ⟨10.1074/jbc.C114.548982⟩. ⟨pasteur-01299773⟩