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 accessAbstract
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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Citations
Cites
Gout-associated uric acid crystals activate the NALP3 inflammasome
Martinon, F., Pétrilli, V., Mayor, A., Tardivel, A., & Tschopp, J. (2006) · Nature · doi:10.1038/nature04516 · Cited by 5,326
Cryopyrin activates the inflammasome in response to toxins and ATP
Mariathasan, S., Weiss, D. S., Newton, K., McBride, J., O'Rourke, K., Roose-Girma, M., Lee, W. P., Weinrauch, Y., Monack, D. M., & Dixit, V. M. (2006) · Nature · doi:10.1038/nature04515 · Cited by 3,080
Hornung, V., Bauernfeind, F., Halle, A., Samstad, E. O., Kono, H., Rock, K. L., Fitzgerald, K. A., & Latz, E. (2008) · Nature Immunology · doi:10.1038/ni.1631 · Cited by 3,065
Innate Immune Activation Through Nalp3 Inflammasome Sensing of Asbestos and Silica
Dostert, C., Pétrilli, V., Van Bruggen, R., Steele, C., Mossman, B. T., & Tschopp, J. (2008) · Science · doi:10.1126/science.1156995 · Cited by 2,658
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Self-citationCytoplasmic flagellin activates caspase-1 and secretion of interleukin 1β via Ipaf
Miao, E. A., Alpuche-Aranda, C. M., Dors, M., Clark, A. E., Bader, M. W., Miller, S. I., & Aderem, A. (2006) · Nature Immunology · doi:10.1038/ni1344 · Cited by 1,127 · cited 2×
“For example, mouse Nlrp1b is a sensor of lethal toxin produced by Bacillus anthracis (12); Nlrc4 detects cytosolic flagellin in cells infected with Salmonella (13, 14), Legionella (15), and Pseudomonas (16, 17).”
BackgroundSutterwala, F. S., Ogura, Y., Szczepanik, M., Lara-Tejero, M., Lichtenberger, G. S., Grant, E. P., Bertin, J., Coyle, A. J., Galán, J. E., Askenase, P. W., et al. (2006) · Immunity · doi:10.1016/j.immuni.2006.02.004 · Cited by 980
The inflammasome: a danger sensing complex triggering innate immunity
Pétrilli, V., Dostert, C., Muruve, D. A., & Tschopp, J. (2007) · Current Opinion in Immunology · doi:10.1016/j.coi.2007.09.002 · Cited by 700
Toll-like receptors — taking an evolutionary approach
Leulier, F., & Lemaitre, B. (2008) · Nature Reviews Genetics · doi:10.1038/nrg2303 · Cited by 581
Regulation of Legionella Phagosome Maturation and Infection through Flagellin and Host Ipaf
Amer, A., Franchi, L., Kanneganti, T.-D., Body-Malapel, M., Özören, N., Brady, G., Meshinchi, S., Jagirdar, R., Gewirtz, A., Akira, S., et al. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m604933200 · Cited by 453
Self-citation
Cited by
Mechanism and Regulation of NLRP3 Inflammasome Activation
He, Y., Hara, H., & Núñez, G. (2016) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2016.09.002 · Cited by 2,759
Self-citationPyroptosis: Mechanisms and Diseases
Yu, P., Zhang, X., Liu, N., Tang, L., Peng, C., & Chen, X. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00507-5 · Cited by 2,353
Bacterial Secretion Systems: An Overview
Green, E. R., & Mecsas, J. (2016) · Microbiology Spectrum · doi:10.1128/microbiolspec.vmbf-0012-2015 · Cited by 1,079
The Inflammasomes in Kidney Disease
Anders, H.-J., & Muruve, D. A. (2011) · Journal of the American Society of Nephrology · doi:10.1681/asn.2010080798 · Cited by 351
Toward targeting inflammasomes: insights into their regulation and activation
Christgen, S., Place, D. E., & Kanneganti, T.-D. (2020) · Cell Research · doi:10.1038/s41422-020-0295-8 · Cited by 281
Metadata
- Authors
- Harder, J., Franchi, L., Muñoz-Planillo, R., Park, J.-H., Reimer, T., & Núñez, G.
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- 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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