| First Author | Costa A | Year | 2012 |
| Journal | J Immunol | Volume | 188 |
| Issue | 4 | Pages | 1953-60 |
| PubMed ID | 22250086 | Mgi Jnum | J:181170 |
| Mgi Id | MGI:5309035 | Doi | 10.4049/jimmunol.1102543 |
| Citation | Costa A, et al. (2012) Activation of the NLRP3 inflammasome by group B streptococci. J Immunol 188(4):1953-60 |
| abstractText | 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-1beta and IL-18. IL-1beta release required both pro-IL-1beta transcription and caspase-1-dependent proteolytic cleavage of intracellular pro-IL-1beta. Dendritic cells lacking the TLR adaptor MyD88, but not those lacking TLR2, were unable to produce pro-IL-1beta mRNA in response to GBS. Pro-IL-1beta cleavage and secretion of the mature IL-1beta 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 beta-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. |
