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Cited by 237

The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.

Activation of the Nlrp3 Inflammasome by Streptococcus pyogenes Requires Streptolysin O and NF-κB Activation but Proceeds Independently of TLR Signaling and P2X7 Receptor

Open access
Harder, Jürgen, Franchi, Luigi, Muñoz-Planillo, Raúl, Park, Jong-Hwan, Reimer, Thornik, Núñez, Gabriel·2009·The Journal of Immunology

Abstract

Macrophages play a crucial role in the innate immune response against the human pathogen Streptococcus pyogenes, yet the innate immune response against the bacterium is poorly characterized. In the present study, we show that caspase-1 activation and IL-1β secretion were induced by live, but not killed, S. pyogenes, and required expression of the pore-forming toxin streptolysin O. Using macrophages deficient in inflammasome components, we found that both NLR family pyrin domain-containing 3 (Nlrp3) and apoptosis-associated speck-like protein (Asc) were crucial for caspase-1 activation and IL-1β secretion, but dispensable for pro-IL-1β induction, in response to S. pyogenes infection. Conversely, macrophages deficient in the essential TLR adaptors Myd88 and Trif showed normal activation of caspase-1, but impaired induction of pro-IL-1β and secretion of IL-1β. Notably, activation of caspase-1 by TLR2 and TLR4 ligands in the presence of streptolysin O required Myd88/Trif, whereas that induced by S. pyogenes was blocked by inhibition of NF-κB. Unlike activation of the Nlrp3 inflammasome by TLR ligands, the induction of caspase-1 activation by S. pyogenes did not require exogenous ATP or the P2X7R. In vivo experiments revealed that Nlrp3 was critical for the production of IL-1β but was not important for survival in a mouse model of S. pyogenes peritoneal infection. These results indicate that caspase-1 activation in response to S. pyogenes infection requires NF-κB and the virulence factor streptolysin O, but proceeds independently of P2X7R and TLR signaling.

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Metadata

Authors
Harder, J., Franchi, L., Muñoz-Planillo, R., Park, J.-H., Reimer, T., & Núñez, G.
Venue
The Journal of Immunology
Published
2009-11-01
Volume
183
Issue
9
Pages
5823-5829
ISSN
  • 0022-1767 (ISSN-L)
  • 1550-6606
OpenAlex
W2155138367
Cited by
237
References
11
FWCI
6.00
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: Activation of the Nlrp3 Inflammasome by Streptococcus pyogenes Requires Streptolysin O and NF-κB Activation but Proceeds Independently of TLR Signaling and P2X7 Receptor. https://app.cochat.ai/papers/10.4049/jimmunol.0900444
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Harder, J., Franchi, L., Muñoz-Planillo, R., Park, J.-H., Reimer, T., & Núñez, G. (2009). Activation of the Nlrp3 Inflammasome by Streptococcus pyogenes Requires Streptolysin O and NF-κB Activation but Proceeds Independently of TLR Signaling and P2X7 Receptor. The Journal of Immunology. https://doi.org/10.4049/jimmunol.0900444

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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