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Activation of the NLRP3 inflammasome by group B streptococci.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2012 Feb 15; Vol. 188 (4), pp. 1953-60. Date of Electronic Publication: 2012 Jan 16. - Publication Year :
- 2012
-
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.
- Subjects :
- Animals
Apoptosis Regulatory Proteins
Bacterial Proteins biosynthesis
CARD Signaling Adaptor Proteins
Carrier Proteins genetics
Caspase 1 genetics
Caspase 1 metabolism
Cytoskeletal Proteins deficiency
Cytoskeletal Proteins genetics
Cytoskeletal Proteins metabolism
Dendritic Cells immunology
Dendritic Cells microbiology
Female
Hemolysin Proteins biosynthesis
Interleukin-18 biosynthesis
Interleukin-18 metabolism
Interleukin-1beta biosynthesis
Interleukin-1beta genetics
Interleukin-1beta metabolism
Macrophages cytology
Macrophages metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Myeloid Differentiation Factor 88 deficiency
Myeloid Differentiation Factor 88 genetics
NLR Family, Pyrin Domain-Containing 3 Protein
RNA, Messenger biosynthesis
Signal Transduction
Streptococcal Infections metabolism
Streptococcus agalactiae metabolism
Streptococcus agalactiae pathogenicity
Toll-Like Receptor 2 deficiency
Toll-Like Receptor 2 genetics
Carrier Proteins immunology
Carrier Proteins metabolism
Inflammasomes immunology
Streptococcal Infections immunology
Streptococcus agalactiae immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 188
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 22250086
- Full Text :
- https://doi.org/10.4049/jimmunol.1102543