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Bacterial RNA:DNA hybrids are activators of the NLRP3 inflammasome
- Source :
- Proceedings of the National Academy of Sciences. 111:7765-7770
- Publication Year :
- 2014
- Publisher :
- Proceedings of the National Academy of Sciences, 2014.
-
Abstract
- Enterohemorrhagic Escherichia coli (EHEC) is an extracellular pathogen that causes hemorrhagic colitis and hemolytic uremic syndrome. The proinflammatory cytokine, interleukin-1β, has been linked to hemolytic uremic syndrome. Here we identify the nucleotide-binding domain and leucine rich repeat containing family, pyrin domain containing 3 (NLRP3) inflammasome as an essential mediator of EHEC-induced IL-1β. Whereas EHEC-specific virulence factors were dispensable for NLRP3 activation, bacterial nucleic acids such as RNA:DNA hybrids and RNA gained cytosolic access and mediated inflammasome-dependent responses. Consistent with a direct role for RNA:DNA hybrids in inflammasome activation, delivery of synthetic EHEC RNA:DNA hybrids into the cytosol triggered NLRP3-dependent responses, and introduction of RNase H, which degrades such hybrids, into infected cells specifically inhibited inflammasome activation. Notably, an E. coli rnhA mutant, which is incapable of producing RNase H and thus harbors increased levels of RNA:DNA hybrid, induced elevated levels of NLRP3-dependent caspase-1 activation and IL-1β maturation. Collectively, these findings identify RNA:DNA hybrids of bacterial origin as a unique microbial trigger of the NLRP3 inflammasome.
- Subjects :
- Ribosomal Proteins
Inflammasomes
Immunoblotting
Interleukin-1beta
Molecular Sequence Data
Caspase 1
DNA, Single-Stranded
Enzyme-Linked Immunosorbent Assay
Biology
medicine.disease_cause
Mice
chemistry.chemical_compound
AIM2
NLR Family, Pyrin Domain-Containing 3 Protein
medicine
Animals
RNase H
Escherichia coli
Mice, Knockout
Microscopy, Confocal
Multidisciplinary
Base Sequence
Escherichia coli Proteins
RNA
Inflammasome
Biological Sciences
Molecular biology
Mice, Inbred C57BL
chemistry
Enterohemorrhagic Escherichia coli
Hemolytic-Uremic Syndrome
Nucleic acid
biology.protein
Carrier Proteins
DNA
medicine.drug
Subjects
Details
- ISSN :
- 10916490 and 00278424
- Volume :
- 111
- Database :
- OpenAIRE
- Journal :
- Proceedings of the National Academy of Sciences
- Accession number :
- edsair.doi.dedup.....9b364fd63f8b1a78d13146323c3986e3