The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.
AIM2 forms a complex with pyrin and ZBP1 to drive PANoptosis and host defence
Open accessAbstract
Inflammasomes are important sentinels of innate immune defence, sensing pathogens and inducing cell death in infected cells1. There are several inflammasome sensors that each detect and respond to a specific pathogen- or damage-associated molecular pattern (PAMP or DAMP, respectively)1. During infection, live pathogens can induce the release of multiple PAMPs and DAMPs, which can simultaneously engage multiple inflammasome sensors2–5. Here we found that AIM2 regulates the innate immune sensors pyrin and ZBP1 to drive inflammatory signalling and a form of inflammatory cell death known as PANoptosis, and provide host protection during infections with herpes simplex virus 1 and Francisella novicida. We also observed that AIM2, pyrin and ZBP1 were members of a large multi-protein complex along with ASC, caspase-1, caspase-8, RIPK3, RIPK1 and FADD, that drove inflammatory cell death (PANoptosis). Collectively, our findings define a previously unknown regulatory and molecular interaction between AIM2, pyrin and ZBP1 that drives assembly of an AIM2-mediated multi-protein complex that we term the AIM2 PANoptosome and comprising multiple inflammasome sensors and cell death regulators. These results advance the understanding of the functions of these molecules in innate immunity and inflammatory cell death, suggesting new therapeutic targets for AIM2-, ZBP1- and pyrin-mediated diseases. AIM2 responds to infection with herpes simplex virus 1 or Francisella novicida by driving assembly of a large multi-protein complex containing multiple inflammasome sensors and cell death regulators.
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Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3
Alexopoulou, L., Holt, A. C., Medzhitov, R., & Flavell, R. A. (2001) · Nature · doi:10.1038/35099560 · Cited by 6,129
AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC
Hornung, V., Ablasser, A., Charrel-Dennis, M., Bauernfeind, F., Horvath, G., Caffrey, D. R., Latz, E., & Fitzgerald, K. A. (2009) · Nature · doi:10.1038/nature07725 · Cited by 2,627
The AIM2 inflammasome is essential for host defense against cytosolic bacteria and DNA viruses
Rathinam, V. A. K., Jiang, Z., Waggoner, S. N., Sharma, S., Cole, L. E., Waggoner, L., Vanaja, S. K., Monks, B. G., Ganesan, S., Latz, E., et al. (2010) · Nature Immunology · doi:10.1038/ni.1864 · Cited by 1,331
Catalytic activity of the caspase-8–FLIPL complex inhibits RIPK3-dependent necrosis
Oberst, A., Dillon, C. P., Weinlich, R., McCormick, L. L., Fitzgerald, P., Pop, C., Hakem, R., Salvesen, G. S., & Green, D. R. (2011) · Nature · doi:10.1038/nature09852 · Cited by 1,278
Kuriakose, T., Man, S. M., Subbarao Malireddi, R. K., Karki, R., Kesavardhana, S., Place, D. E., Neale, G., Vogel, P., & Kanneganti, T.-D. (2016) · Science Immunology · doi:10.1126/sciimmunol.aag2045 · Cited by 818
Self-citationThe AIM2 inflammasome is critical for innate immunity to Francisella tularensis
Fernandes-Alnemri, T., Yu, J.-W., Juliana, C., Solorzano, L., Kang, S., Wu, J., Datta, P., McCormick, M., Huang, L., McDermott, E., et al. (2010) · Nature Immunology · doi:10.1038/ni.1859 · Cited by 732
RIPK1 inhibits ZBP1-driven necroptosis during development
Newton, K., Wickliffe, K. E., Maltzman, A., Dugger, D. L., Strasser, A., Pham, V. C., Lill, J. R., Roose-Girma, M., Warming, S., Solon, M., et al. (2016) · Nature · doi:10.1038/nature20559 · Cited by 390
Survival Function of the FADD-CASPASE-8-cFLIPL Complex
Dillon, C. P., Oberst, A., Weinlich, R., Janke, L. J., Kang, T.-B., Ben-Moshe, T., Mak, T. W., Wallach, D., & Green, D. R. (2012) · Cell Reports · doi:10.1016/j.celrep.2012.03.010 · Cited by 331
Dietary modulation of the microbiome affects autoinflammatory disease
Lukens, J. R., Gurung, P., Vogel, P., Johnson, G. R., Carter, R. A., McGoldrick, D. J., Bandi, S. R., Calabrese, C. R., Walle, L. V., Lamkanfi, M., et al. (2014) · Nature · doi:10.1038/nature13788 · Cited by 314
Self-citationIRGB10 Liberates Bacterial Ligands for Sensing by the AIM2 and Caspase-11-NLRP3 Inflammasomes
Man, S. M., Karki, R., Sasai, M., Place, D. E., Kesavardhana, S., Temirov, J., Frase, S., Zhu, Q., Malireddi, R. K. S., Kuriakose, T., et al. (2016) · Cell · doi:10.1016/j.cell.2016.09.012 · Cited by 312
Self-citation
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A 360° view of the inflammasome: Mechanisms of activation, cell death, and diseases
Barnett, K. C., Li, S., Liang, K., & Ting, J. P.-Y. (2023) · Cell · doi:10.1016/j.cell.2023.04.025 · Cited by 458
Lee, E., Song, C.-H., Bae, S.-J., Ha, K.-T., & Karki, R. (2023) · Experimental & Molecular Medicine · doi:10.1038/s12276-023-01069-y · Cited by 164
Self-citationViral sepsis: diagnosis, clinical features, pathogenesis, and clinical considerations
Xu, J.-Q., Zhang, W.-Y., Fu, J.-J., Fang, X.-Z., Gao, C.-G., Li, C., Yao, L., Li, Q.-L., Yang, X.-B., Ren, L.-H., et al. (2024) · Military Medical Research · doi:10.1186/s40779-024-00581-0 · Cited by 37
Centofanti, E., Oyler-Yaniv, A., & Oyler-Yaniv, J. (2025) · Molecular Biology of the Cell · doi:10.1091/mbc.e24-10-0438 · Cited by 4
Metadata
- Authors
- Lee, S., Karki, R., Wang, Y., Nguyen, L. N., Kalathur, R. C., & Kanneganti, T.-D.
- Venue
- Nature
- Published
- 2021-09-01
- Volume
- 597
- Issue
- 7876
- Pages
- 415-419
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W3197986920
- Cited by
- 783
- References
- 11
- FWCI
- 25.43
- Type
- journal article
- Language
- en
- Open access
- green
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