Abstract
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.
© 2014 by The American Society for Biochemistry and Molecular Biology, Inc.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Bacterial Proteins / metabolism*
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Carrier Proteins / metabolism*
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Hemolysin Proteins / metabolism*
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Humans
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Inflammasomes / metabolism*
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Interleukin-1beta / biosynthesis*
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Interleukin-1beta / metabolism
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Lysosomes / metabolism
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Lysosomes / microbiology
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Macrophages / cytology
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Macrophages / metabolism*
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Macrophages / microbiology
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Mice
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NLR Family, Pyrin Domain-Containing 3 Protein
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Phagosomes / metabolism
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Phagosomes / microbiology
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RNA, Bacterial / metabolism*
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Streptococcus agalactiae / metabolism
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Streptococcus agalactiae / physiology*
Substances
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Bacterial Proteins
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Carrier Proteins
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Hemolysin Proteins
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Inflammasomes
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Interleukin-1beta
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NLR Family, Pyrin Domain-Containing 3 Protein
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NLRP3 protein, human
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Nlrp3 protein, mouse
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RNA, Bacterial
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streptococcal group B hemolysin