title: Activation of the NLRP3 inflammasome by group B streptococci.
abstract: Group B Streptococcus (GBS) is a frequent agent of life-threatening sepsis and meningitis in neonates and adults with predisposing conditions. We tested the hypothesis that activation of the inflammasome, an inflammatory signaling complex, is involved in host defenses against this pathogen. We show in this study that murine bone marrow-derived conventional dendritic cells responded to GBS by secreting IL-1β and IL-18. IL-1β release required both pro-IL-1β transcription and caspase-1-dependent proteolytic cleavage of intracellular pro-IL-1β. Dendritic cells lacking the TLR adaptor MyD88, but not those lacking TLR2, were unable to produce pro-IL-1β mRNA in response to GBS. Pro-IL-1β cleavage and secretion of the mature IL-1β form depended on the NOD-like receptor family, pyrin domain containing 3 (NLRP3) sensor and the apoptosis-associated speck-like protein containing a caspase activation and recruitment domain adaptor. Moreover, activation of the NLRP3 inflammasome required GBS expression of β-hemolysin, an important virulence factor. We further found that mice lacking NLRP3, apoptosis-associated speck-like protein, or caspase-1 were considerably more susceptible to infection than wild-type mice. Our data link the production of a major virulence factor by GBS with the activation of a highly effective anti-GBS response triggered by the NLRP3 inflammasome.
authors.affiliation: Elie Metchnikoff Department, University of Messina, Messina I-98125, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Costa
authors.forename: Rahul
authors.initials: R
authors.lastname: Gupta
authors.forename: Giacomo
authors.initials: G
authors.lastname: Signorino
authors.forename: Antonio
authors.initials: A
authors.lastname: Malara
authors.forename: Francesco
authors.initials: F
authors.lastname: Cardile
authors.forename: Carmelo
authors.initials: C
authors.lastname: Biondo
authors.forename: Angelina
authors.initials: A
authors.lastname: Midiri
authors.forename: Roberta
authors.initials: R
authors.lastname: Galbo
authors.forename: Patrick
authors.initials: P
authors.lastname: Trieu-Cuot
authors.forename: Salvatore
authors.initials: S
authors.lastname: Papasergi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Teti
authors.forename: Philipp
authors.initials: P
authors.lastname: Henneke
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Mancuso
authors.forename: Douglas T
authors.initials: DT
authors.lastname: Golenbock
authors.forename: Concetta
authors.initials: C
authors.lastname: Beninati
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins; D001426:Bacterial Proteins / Q000096:biosynthesis; D053468:CARD Signaling Adaptor Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D020170:Caspase 1 / Q000235:genetics / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000382:microbiology; D005260:Female; D006460:Hemolysin Proteins / Q000096:biosynthesis; D058847:Inflammasomes / Q000276:immunology*; D020382:Interleukin-18 / Q000096:biosynthesis / Q000378:metabolism; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency / Q000235:genetics; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D012333:RNA, Messenger / Q000096:biosynthesis; D015398:Signal Transduction; D013290:Streptococcal Infections / Q000276:immunology* / Q000378:metabolism; D013292:Streptococcus agalactiae / Q000276:immunology* / Q000378:metabolism / Q000472:pathogenicity; D051195:Toll-Like Receptor 2 / Q000172:deficiency / Q000235:genetics
chemical_list: D051017:Apoptosis Regulatory Proteins; D001426:Bacterial Proteins; D053468:CARD Signaling Adaptor Proteins; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D006460:Hemolysin Proteins; D058847:Inflammasomes; D020382:Interleukin-18; D053583:Interleukin-1beta; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; C498534:Pycard protein, mouse; D012333:RNA, Messenger; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; C071495:streptococcal group B hemolysin; D020170:Caspase 1