AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA
Open accessAbstract
Host- and pathogen-associated cytoplasmic double-stranded DNA triggers the activation of a NALP3 (also known as cryopyrin and NLRP3)-independent inflammasome, which activates caspase-1 leading to maturation of pro-interleukin-1beta and inflammation. The nature of the cytoplasmic-DNA-sensing inflammasome is currently unknown. Here we show that AIM2 (absent in melanoma 2), an interferon-inducible HIN-200 family member that contains an amino-terminal pyrin domain and a carboxy-terminal oligonucleotide/oligosaccharide-binding domain, senses cytoplasmic DNA by means of its oligonucleotide/oligosaccharide-binding domain and interacts with ASC (apoptosis-associated speck-like protein containing a CARD) through its pyrin domain to activate caspase-1. The interaction of AIM2 with ASC also leads to the formation of the ASC pyroptosome, which induces pyroptotic cell death in cells containing caspase-1. Knockdown of AIM2 by short interfering RNA reduced inflammasome/pyroptosome activation by cytoplasmic DNA in human and mouse macrophages, whereas stable expression of AIM2 in the non-responsive human embryonic kidney 293T cell line conferred responsiveness to cytoplasmic DNA. Our results show that cytoplasmic DNA triggers formation of the AIM2 inflammasome by inducing AIM2 oligomerization. This study identifies AIM2 as an important inflammasome component that senses potentially dangerous cytoplasmic DNA, leading to activation of the ASC pyroptosome and caspase-1.
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The AIM2 inflammasome has been shown to recognize cytoplasmic double-stranded DNA (dsDNA) that is not necessarily microbial in origin, resulting in caspase 1 activation and IL-1β secretion.
“The AIM2 inflammasome has been recently shown to recognize cytoplasmic double-stranded DNA (dsDNA) that is not necessarily microbial in origin, resulting in caspase 1 activation and IL-1β secretion48–50.”
From Sterile inflammation: sensing and reacting to damage (2010) · cites this paper as [49]
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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 · see citing works
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 · see citing works
The NALP3 inflammasome is involved in the innate immune response to amyloid-β
Halle, A., Hornung, V., Petzold, G. C., Stewart, C. R., Monks, B. G., Reinheckel, T., Fitzgerald, K. A., Latz, E., Moore, K. J., & Golenbock, D. T. (2008) · Nature Immunology · doi:10.1038/ni.1636 · Cited by 2,441 · see citing works
Agostini, L., Martinon, F., Burns, K., McDermott, M. F., Hawkins, P. N., & Tschopp, J. (2004) · Immunity · doi:10.1016/s1074-7613(04)00046-9 · Cited by 1,768 · see citing works
Crucial role for the Nalp3 inflammasome in the immunostimulatory properties of aluminium adjuvants
Eisenbarth, S. C., Colegio, O. R., O’Connor, W., Sutterwala, F. S., & Flavell, R. A. (2008) · Nature · doi:10.1038/nature06939 · Cited by 1,542 · see citing works
Fernandes-Alnemri, T., Wu, J., Yu, J.-W., Datta, P., Miller, B., Jankowski, W., Rosenberg, S., Zhang, J., & Alnemri, E. S. (2007) · Cell Death & Differentiation · doi:10.1038/sj.cdd.4402194 · Cited by 1,026 · see citing works
Self-citationThe inflammasome recognizes cytosolic microbial and host DNA and triggers an innate immune response
Muruve, D. A., Pétrilli, V., Zaiss, A. K., White, L. R., Clark, S. A., Ross, P. J., Parks, R. J., & Tschopp, J. (2008) · Nature · doi:10.1038/nature06664 · Cited by 936 · see citing works
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 · see citing works
The PYRIN-CARD Protein ASC Is an Activating Adaptor for Caspase-1
Srinivasula, S. M., Poyet, J.-L., Razmara, M., Datta, P., Zhang, Z., & Alnemri, E. S. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.c200179200 · Cited by 573 · see citing works
Self-citationFranchi, L., & Núñez, G. (2008) · European Journal of Immunology · doi:10.1002/eji.200838549 · Cited by 452 · see citing works
Cryopyrin and pyrin activate caspase-1, but not NF-κB, via ASC oligomerization
Yu, J., Wu, J., Zhang, Z., Datta, P., Ibrahimi, I., Taniguchi, S., Sagara, J., Fernandes‐Alnemri, T., & Alnemri, E. S. (2005) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401734 · Cited by 347 · see citing works
Self-citationPyrin Activates the ASC Pyroptosome in Response to Engagement by Autoinflammatory PSTPIP1 Mutants
Yu, J., Fernandes‐Alnemri, T., Datta, P., Wu, J., Juliana, C. A., Solórzano, L., McCormick, M., Zhang, Z., & Alnemri, E. S. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.08.029 · Cited by 287 · see citing works
Self-citationDeyoung, K. L., Ray, M. E., Su, Y. A., Anzick, S. L., Johnstone, R. W., Trapani, J. A., Meltzer, P. S., & Trent, J. M. (1997) · Oncogene · doi:10.1038/sj.onc.1201206 · Cited by 268 · see citing works
The HIN-200 family: More than interferon-inducible genes?
Ludlow, L. E. A., Johnstone, R. W., & Clarke, C. J. P. (2005) · Experimental Cell Research · doi:10.1016/j.yexcr.2005.03.032 · Cited by 170 · see citing works
Interferon-inducible Ifi200-family genes in systemic lupus erythematosus
Choubey, D., & Panchanathan, R. (2008) · Immunology Letters · doi:10.1016/j.imlet.2008.06.001 · Cited by 109 · see citing works
The HIN domain of IFI-200 proteins consists of two OB folds
Albrecht, M., Choubey, D., & Lengauer, T. (2004) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2004.12.056 · Cited by 85 · see citing works
Chapter Thirteen Assembly, Purification, and Assay of the Activity of the ASC Pyroptosome
Fernandes‐Alnemri, T., & Alnemri, E. S. (2008) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(08)01413-4 · Cited by 69 · see citing works
Self-citationMeier, O. C., Gastaldelli, M., Boucke, K., Hemmi, S., & Greber, U. F. (2005) · Journal of Virology · doi:10.1128/jvi.79.4.2604-2613.2005 · Cited by 41 · see citing works
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Schroder, K., & Tschopp, J. (2010) · Cell · doi:10.1016/j.cell.2010.01.040 · Cited by 5,475 · see citing works
Inflammasomes: mechanism of assembly, regulation and signalling
Broz, P., & Dixit, V. M. (2016) · Nature Reviews Immunology · doi:10.1038/nri.2016.58 · Cited by 3,500 · see citing works
Inflammasomes: mechanism of action, role in disease, and therapeutics
Guo, H., Callaway, J. B., & Ting, J. P.-Y. (2015) · Nature Medicine · doi:10.1038/nm.3893 · Cited by 3,340 · see citing works
Sterile inflammation: sensing and reacting to damage
Chen, G. Y., & Nuñez, G. (2010) · Nature Reviews Immunology · doi:10.1038/nri2873 · Cited by 3,051 · see citing works
Bauernfeind, F. G., Horvath, G. L., Stutz, A., Alnemri, E. S., MacDonald, K. L., Speert, D. P., Fernandes‐Alnemri, T., Wu, J., Monks, B. G., Fitzgerald, K. A., et al. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0901363 · Cited by 3,006 · see citing works
Self-citationA small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases
Coll, R. C., Robertson, A. A. B., Chae, J. J., Higgins, S. C., Muñoz-Planillo, R., Inserra, M. C., Vetter, I., Dungan, L. S., Monks, B. G., Stutz, A., et al. (2015) · Nature Medicine · doi:10.1038/nm.3806 · Cited by 2,849 · see citing works
STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity
Ishikawa, H., Ma, Z., & Barber, G. N. (2009) · Nature · doi:10.1038/nature08476 · Cited by 2,759 · see citing works
Caspase Functions in Cell Death and DiseasePreprint
McIlwain, D. R., Berger, T., & Mak, T. W. (2013) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a008656 · Cited by 2,607 · see citing works
Non-canonical inflammasome activation targets caspase-11
Kayagaki, N., Warming, S., Lamkanfi, M., Walle, L. V., Louie, S., Dong, J., Newton, K., Qu, Y., Liu, J., Heldens, S., et al. (2011) · Nature · doi:10.1038/nature10558 · Cited by 2,530 · see citing works
Galluzzi, L., Vitale, I., Abrams, J. M., Alnemri, E. S., Baehrecke, E. H., Blagosklonny, M. V., Dawson, T. M., Dawson, V. L., El-Deiry, W. S., Fulda, S., et al. (2012) · Cell Death & Differentiation · doi:10.1038/cdd.2011.96 · Cited by 2,421 · see citing works
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 · see citing works
Pathogen Recognition by the Innate Immune System
Kumar, H., Kawai, T., & Akira, S. (2011) · International Reviews of Immunology · doi:10.3109/08830185.2010.529976 · Cited by 2,264 · see citing works
Inflammasomes in health and disease
Strowig, T., Henao-Mejia, J., Elinav, E., & Flavell, R. (2012) · Nature · doi:10.1038/nature10759 · Cited by 2,230 · see citing works
Franchi, L., Eigenbrod, T., Muñoz-Planillo, R., & Nuñez, G. (2009) · Nature Immunology · doi:10.1038/ni.1703 · Cited by 1,834 · see citing works
Man, S. M., Karki, R., & Kanneganti, T. (2017) · Immunological Reviews · doi:10.1111/imr.12534 · Cited by 1,659 · see citing works
IFI16 is an innate immune sensor for intracellular DNA
Unterholzner, L., Keating, S. E., Baran, M., Horan, K. A., Jensen, S. B., Sharma, S., Sirois, C. M., Jin, T., Latz, E., Xiao, T. S., et al. (2010) · Nature Immunology · doi:10.1038/ni.1932 · Cited by 1,643 · see citing works
Understanding the mechanism of IL-1β secretion
Lopez-Castejon, G., & Brough, D. (2011) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2011.10.001 · Cited by 1,519 · see citing works
Rogers, C., Fernandes-Alnemri, T., Mayes, L., Alnemri, D., Cingolani, G., & Alnemri, E. S. (2017) · Nature Communications · doi:10.1038/ncomms14128 · Cited by 1,510 · see citing works
“In some experiments, cell culture supernatants were precipitated by methanol/chloroform as described previously 24,59 .”
Self-citationInnate Immune Pattern Recognition: A Cell Biological Perspective
Brubaker, S. W., Bonham, K. S., Zanoni, I., & Kagan, J. C. (2015) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032414-112240 · Cited by 1,475 · see citing works
DNA sensing by the cGAS–STING pathway in health and disease
Motwani, M., Pesiridis, S., & Fitzgerald, K. A. (2019) · Nature Reviews Genetics · doi:10.1038/s41576-019-0151-1 · Cited by 1,467 · see citing works
Shi, C.-S., Shenderov, K., Huang, N.-N., Kabat, J., Abu-Asab, M., Fitzgerald, K. A., Sher, A., & Kehrl, J. H. (2012) · Nature Immunology · doi:10.1038/ni.2215 · Cited by 1,367 · see citing works
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 · see citing works
Innate Immune Sensing and Signaling of Cytosolic Nucleic Acids
Wu, J., & Chen, Z. J. (2014) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032713-120156 · Cited by 1,179 · see citing works
Self-citationCaspase‐1‐induced pyroptotic cell death
Miao, E. A., Rajan, J. V., & Aderem, A. A. (2011) · Immunological Reviews · doi:10.1111/j.1600-065x.2011.01044.x · Cited by 1,139 · see citing works
Inflammasome Complexes: Emerging Mechanisms and Effector Functions
Rathinam, V. A. K., & Fitzgerald, K. A. (2016) · Cell · doi:10.1016/j.cell.2016.03.046 · Cited by 1,109 · see citing works
Gao, P., Ascano, M., Wu, Y., Barchet, W., Gaffney, B. L., Zillinger, T., Serganov, A. A., Liu, Y., Jones, R. A., Hartmann, G., et al. (2013) · Cell · doi:10.1016/j.cell.2013.04.046 · Cited by 1,101 · see citing works
Regulation of inflammasome activation
Man, S. M., & Kanneganti, T. (2015) · Immunological Reviews · doi:10.1111/imr.12296 · Cited by 1,071 · see citing works
Mitochondrial control of inflammation
Marchi, S., Guilbaud, E., Tait, S. W. G., Yamazaki, T., & Galluzzi, L. (2023) · Nature Reviews Immunology · doi:10.1038/s41577-022-00760-x · Cited by 1,027 · see citing works
Pyroptotic cell death defends against intracellular pathogens
Jorgensen, I., & Miao, E. A. (2015) · Immunological Reviews · doi:10.1111/imr.12287 · Cited by 1,021 · see citing works
Emerging connectivity of programmed cell death pathways and its physiological implications
Bedoui, S., Herold, M. J., & Strasser, A. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-0270-8 · Cited by 986 · see citing works
Inflammasomes and Their Roles in Health and Disease
Lamkanfi, M., & Dixit, V. M. (2012) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-101011-155745 · Cited by 935 · see citing works
Caspases in Cell Death, Inflammation, and Pyroptosis
Kesavardhana, S., Malireddi, R. K. S., & Kanneganti, T. (2020) · Annual Review of Immunology · doi:10.1146/annurev-immunol-073119-095439 · Cited by 927 · see citing works
Ablasser, A., Bauernfeind, F. G., Hartmann, G., Latz, E., Fitzgerald, K. A., & Hornung, V. (2009) · Nature Immunology · doi:10.1038/ni.1779 · Cited by 892 · see citing works
Targeting Toll-like receptors: emerging therapeutics?
Hennessy, E. J., Parker, A. E., & O'Neill, L. A. J. (2010) · Nature Reviews Drug Discovery · doi:10.1038/nrd3203 · Cited by 890 · see citing works
Structural mechanism of cytosolic DNA sensing by cGAS
Çivril, F., Deimling, T., Mann, C. C. D. O., Ablasser, A., Moldt, M., Witte, G., Hornung, V., & Hopfner, K. (2013) · Nature · doi:10.1038/nature12305 · Cited by 888 · see citing works
The helicase DDX41 senses intracellular DNA mediated by the adaptor STING in dendritic cells
Zhang, Z., Yuan, B., Bao, M., Lu, N., Kim, T., & Liu, Y. (2011) · Nature Immunology · doi:10.1038/ni.2091 · Cited by 874 · see citing works
DAMPs, PAMPs, and LAMPs in Immunity and Sterile Inflammation
Zindel, J., & Kubes, P. (2019) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathmechdis-012419-032847 · Cited by 874 · see citing works
The Sterile Inflammatory Response
Rock, K. L., Latz, E., Ontiveros, F., & Kono, H. (2010) · Annual Review of Immunology · doi:10.1146/annurev-immunol-030409-101311 · Cited by 865 · see citing works
Rogers, C., Erkes, D. A., Nardone, A., Aplin, A. E., Fernandes‐Alnemri, T., & Alnemri, E. S. (2019) · Nature Communications · doi:10.1038/s41467-019-09397-2 · Cited by 834 · see citing works
Self-citationAllen, I. C., TeKippe, E. M., Woodford, R.-M. T., Uronis, J. M., Holl, E. K., Rogers, A. B., Herfarth, H. H., Jobin, C., & Ting, J. P.-Y. (2010) · Journal of Experimental Medicine · doi:10.1084/jem.20100050 · Cited by 826 · see citing works
The inflammasome: an integrated view
Gross, O., Thomas, C. J., Guarda, G., & Tschopp, J. (2011) · Immunological Reviews · doi:10.1111/j.1600-065x.2011.01046.x · Cited by 778 · see citing works
Non-transcriptional Priming and Deubiquitination Regulate NLRP3 Inflammasome Activation
Juliana, C. A., Fernandes‐Alnemri, T., Kang, S., Farias, A., Qin, F., & Alnemri, E. S. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.407130 · Cited by 771 · see citing works
Self-citationPaludan, S. R., & Bowie, A. (2013) · Immunity · doi:10.1016/j.immuni.2013.05.004 · Cited by 764 · see citing works
Ion Channels in Innate and Adaptive Immunity
Feske, S., Wulff, H., & Skolnik, E. Y. (2015) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032414-112212 · Cited by 764 · see citing works
Neuroinflammation: The role and consequences
Lyman, M., Lloyd, D. G., Ji, X., Vizcaychipi, M. P., & Ma, D. (2013) · Neuroscience Research · doi:10.1016/j.neures.2013.10.004 · Cited by 740 · see citing works
Mechanism of NLRP3 inflammasome activation
Sutterwala, F. S., Haasken, S., & Cassel, S. L. (2014) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12458 · Cited by 736 · see citing works
The cell biology of inflammasomes: Mechanisms of inflammasome activation and regulation
Sharma, D., & Kanneganti, T. (2016) · The Journal of Cell Biology · doi:10.1083/jcb.201602089 · Cited by 733 · see citing works
The 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 · see citing works
Self-citationDeubiquitination of NLRP3 by BRCC3 Critically Regulates Inflammasome Activity
Py, B. F., Kim, M.-S., Vakifahmetoglu-Norberg, H., & Yuan, J. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.11.009 · Cited by 718 · see citing works
Burdette, B. E., Esparza, A. N., Zhu, H., & Wang, S. (2021) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2021.02.006 · Cited by 710 · see citing works
Kerur, N., Veettil, M. V., Sharma-Walia, N., Bottero, V., Sadagopan, S., Otageri, P., & Chandran, B. (2011) · Cell Host & Microbe · doi:10.1016/j.chom.2011.04.008 · Cited by 702 · see citing works
Converging roles of caspases in inflammasome activation, cell death and innate immunity
Man, S. M., & Kanneganti, T. (2015) · Nature reviews. Immunology · doi:10.1038/nri.2015.7 · Cited by 701 · see citing works
Inflammasome activation and IL-1β and IL-18 processing during infection
van de Veerdonk, F. L., Netea, M. G., Dinarello, C. A., & Joosten, L. A. B. (2011) · Trends in Immunology · doi:10.1016/j.it.2011.01.003 · Cited by 693 · see citing works
PtdIns4P on dispersed trans-Golgi network mediates NLRP3 inflammasome activation
Chen, J., & Chen, Z. J. (2018) · Nature · doi:10.1038/s41586-018-0761-3 · Cited by 692 · see citing works
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Kauppinen, A., Paterno, J. J., Błasiak, J., Salminen, A., & Kaarniranta, K. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2147-8 · Cited by 660 · see citing works
Diverging inflammasome signals in tumorigenesis and potential targeting
Karki, R., & Kanneganti, T. (2019) · Nature reviews. Cancer · doi:10.1038/s41568-019-0123-y · Cited by 641 · see citing works
Gaidt, M. M., Ebert, T. S., Chauhan, D., Ramshorn, K., Pinci, F., Zuber, S., O’Duill, F., Schmid-Burgk, J. L., Hoss, F., Buhmann, R., et al. (2017) · Cell · doi:10.1016/j.cell.2017.09.039 · Cited by 638 · see citing works
Walsh, J. G., Muruve, D. A., & Power, C. (2014) · Nature Reviews Neuroscience · doi:10.1038/nrn3638 · Cited by 637 · see citing works
Influenza virus activates inflammasomes via its intracellular M2 ion channel
Ichinohe, T., Pang, I. K., & Iwasaki, A. (2010) · Nature Immunology · doi:10.1038/ni.1861 · Cited by 632 · see citing works
Bauernfeind, F., Bartok, E., Rieger, A., Franchi, L., Núñez, G., & Hornung, V. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1100613 · Cited by 617 · see citing works
Anti-inflammatory Compounds Parthenolide and Bay 11-7082 Are Direct Inhibitors of the Inflammasome
Juliana, C. A., Fernandes‐Alnemri, T., Wu, J., Datta, P., Solórzano, L., Yu, J., Meng, R., Quong, A. A., Latz, E., Scott, C. P., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.082305 · Cited by 617 · see citing works
Self-citationZheng, M., & Kanneganti, T. (2020) · Immunological Reviews · doi:10.1111/imr.12909 · Cited by 591 · see citing works
IRF7: activation, regulation, modification and function
Ning, S., Pagano, J. S., & Barber, G. N. (2011) · Genes and Immunity · doi:10.1038/gene.2011.21 · Cited by 590 · see citing works
Tetherin Inhibits HIV-1 Release by Directly Tethering Virions to Cells
Pérez-Caballero, D., Zang, T. M., Ebrahimi, A., McNatt, M. W., Gregory, D. A., Johnson, M. C., & Bieniasz, P. D. (2009) · Cell · doi:10.1016/j.cell.2009.08.039 · Cited by 590 · see citing works
Discriminating self from non-self in nucleic acid sensing
Schlee, M., & Hartmann, G. (2016) · Nature reviews. Immunology · doi:10.1038/nri.2016.78 · Cited by 587 · see citing works
Pathogen recognition in the innate immune response
Kumar, H., Kawai, T., & Akira, S. (2009) · Biochemical Journal · doi:10.1042/bj20090272 · Cited by 586 · see citing works
Nucleic acid recognition by the innate immune system
Barbalat, R., Ewald, S. E., Mouchess, M. L., & Barton, G. M. (2011) · Annual Review of Immunology · doi:10.1146/annurev-immunol-031210-101340 · Cited by 577 · see citing works
Jin, T., Perry, A., Jiang, J., Smith, P. T., Curry, J. A., Unterholzner, L., Jiang, Z., Horvath, G. L., Rathinam, V. A. K., Johnstone, R. W., et al. (2012) · Immunity · doi:10.1016/j.immuni.2012.02.014 · Cited by 571 · see citing works
Hise, A. G., Tomalka, J. A., Ganesan, S., Patel, K., Hall, B. A., Brown, G. D., & Fitzgerald, K. A. (2009) · Cell Host & Microbe · doi:10.1016/j.chom.2009.05.002 · Cited by 568 · see citing works
Interleukin-18 in Health and Disease
Yasuda, K., Nakanishi, K., & Tsutsui, H. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20030649 · Cited by 564 · see citing works
Jeremiah, N., Neven, B., Gentili, M., Callebaut, I., Maschalidi, S., Stolzenberg, M.-C., Goudin, N., Frémond, M.-L., Nitschke, P., Molina, T. J., et al. (2014) · Journal of Clinical Investigation · doi:10.1172/jci79100 · Cited by 562 · see citing works
Samir, P., Malireddi, R. K. S., & Kanneganti, T.-D. (2020) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2020.00238 · Cited by 557 · see citing works
Redundant roles for inflammasome receptors NLRP3 and NLRC4 in host defense against <i>Salmonella</i>
Broz, P., Newton, K., Lamkanfi, M., Mariathasan, S., Dixit, V. M., & Monack, D. M. (2010) · Journal of Experimental Medicine · doi:10.1084/jem.20100257 · Cited by 549 · see citing works
DNA released from dying host cells mediates aluminum adjuvant activity
Marichal, T., Ohata, K., Bedoret, D., Mesnil, C., Sabatel, C. M., Kobiyama, K., Lekeux, P. M., Coban, C., Akira, S., Ishii, K. J., et al. (2011) · Nature Medicine · doi:10.1038/nm.2403 · Cited by 538 · see citing works
Poeck, H., Bscheider, M., Groß, O., Finger, K., Roth, S., Rebsamen, M., Hannesschläger, N., Schlee, M., Rothenfußer, S., Barchet, W., et al. (2009) · Nature Immunology · doi:10.1038/ni.1824 · Cited by 518 · see citing works
Programmed cell death and the immune system
Nagata, S., & Tanaka, M. (2017) · Nature reviews. Immunology · doi:10.1038/nri.2016.153 · Cited by 518 · see citing works
Mack, M. (2017) · Matrix Biology · doi:10.1016/j.matbio.2017.11.010 · Cited by 516 · see citing works
Emerging Activators and Regulators of Inflammasomes and Pyroptosis
Xue, Y., Tuipulotu, D. E., Tan, W. H., Kay, C., & Man, S. M. (2019) · Trends in Immunology · doi:10.1016/j.it.2019.09.005 · Cited by 513 · see citing works
GBP5 Promotes NLRP3 Inflammasome Assembly and Immunity in Mammals
Shenoy, A. R., Wellington, D. A., Kumar, P., Kassa, H. T., Booth, C. J., Cresswell, P., & MacMicking, J. D. (2012) · Science · doi:10.1126/science.1217141 · Cited by 512 · see citing works
Vance, R. E., Isberg, R. R., & Portnoy, D. A. (2009) · Cell Host & Microbe · doi:10.1016/j.chom.2009.06.007 · Cited by 512 · see citing works
IFI16 DNA Sensor Is Required for Death of Lymphoid CD4 T Cells Abortively Infected with HIV
Monroe, K. M., Yang, Z., Johnson, J. R., Geng, X., Doitsh, G., Krogan, N. J., & Greene, W. C. (2014) · Science · doi:10.1126/science.1243640 · Cited by 511 · see citing works
AIM2 and NLRP3 inflammasomes activate both apoptotic and pyroptotic death pathways via ASC
Sagulenko, V., Thygesen, S. J., Sester, D. P., Idris, A., Cridland, J. A., Vajjhala, P. R., Roberts, T. L., Schroder, K., Vince, J. E., Hill, J. M., et al. (2013) · Cell Death and Differentiation · doi:10.1038/cdd.2013.37 · Cited by 511 · see citing works
The lncRNA Neat1 promotes activation of inflammasomes in macrophages
Zhang, P., Cao, L., Zhou, R., Yang, X., & Wu, M. (2019) · Nature Communications · doi:10.1038/s41467-019-09482-6 · Cited by 503 · see citing works
IL-1β Processing in Host Defense: Beyond the Inflammasomes
Netea, M. G., Simon, A., van de Veerdonk, F. L., Kullberg, B. J., van der Meer, J. W. M., & Joosten, L. A. B. (2010) · PLoS Pathogens · doi:10.1371/journal.ppat.1000661 · Cited by 496 · see citing works
The Ubiquitin Ligase TRIM56 Regulates Innate Immune Responses to Intracellular Double-Stranded DNA
Tsuchida, T., Zou, J. P., Saitoh, T., Kumar, H., Abe, T., Matsuura, Y., Kawai, T., & Akira, S. (2010) · Immunity · doi:10.1016/j.immuni.2010.10.013 · Cited by 488 · see citing works
Absent in melanoma 2 is required for innate immune recognition of Francisella tularensis
Jones, J. W. M., Kayagaki, N., Brož, P., Henry, T., Newton, K., O’Rourke, K. M., Chan, S. B., Dong, J. J., Qu, Y., Roose-Girma, M., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1003738107 · Cited by 487 · see citing works
Platnich, J. M., & Muruve, D. A. (2019) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2019.02.008 · Cited by 475 · see citing works
Reactive oxygen species at the crossroads of inflammasome and inflammation
Harijith, A. K., Ebenezer, D. L., & Natarajan, V. (2014) · Frontiers in Physiology · doi:10.3389/fphys.2014.00352 · Cited by 474 · see citing works
Newly described pattern recognition receptors team up against intracellular pathogens
Brož, P., & Monack, D. M. (2013) · Nature reviews. Immunology · doi:10.1038/nri3479 · Cited by 459 · see citing works
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 · see citing works
The inflammasomes: mechanisms of activation and function
Latz, E. (2010) · Current Opinion in Immunology · doi:10.1016/j.coi.2009.12.004 · Cited by 455 · see citing works
Barbalat, R., Lau, L., Locksley, R. M., & Barton, G. M. (2009) · Nature Immunology · doi:10.1038/ni.1792 · Cited by 453 · see citing works
Inflammasome activation and assembly at a glance
Malik, A., & Kanneganti, T. (2017) · Journal of Cell Science · doi:10.1242/jcs.207365 · Cited by 451 · see citing works
Manipulation of Host Cell Death Pathways during Microbial Infections
Lamkanfi, M., & Dixit, V. M. (2010) · Cell Host & Microbe · doi:10.1016/j.chom.2010.06.007 · Cited by 450 · see citing works
Detection of Microbial Infections Through Innate Immune Sensing of Nucleic Acids
Tan, J. X., Sun, L., Chen, J., & Chen, Z. J. (2018) · Annual Review of Microbiology · doi:10.1146/annurev-micro-102215-095605 · Cited by 437 · see citing works
Cytosolic DNA Triggers Inflammasome Activation in Keratinocytes in Psoriatic Lesions
Dombrowski, Y., Perić, M., Koglin, S., Kammerbauer, C., Göß, C., Anz, D., Simanski, M., Gläser, R., Harder, J., Hornung, V., et al. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3002001 · Cited by 433 · see citing works
DNA Repair Pathway Choices in CRISPR-Cas9-Mediated Genome Editing
Xue, C., & Greene, E. C. (2021) · Trends in Genetics · doi:10.1016/j.tig.2021.02.008 · Cited by 431 · see citing works
Lee, E., Hwang, I., Park, S., Hong, S., Hwang, B., Cho, Y., Son, J., & Yu, J.-W. (2019) · Cell Death & Differentiation · doi:10.1038/s41418-018-0124-5 · Cited by 431 · see citing works
Self-citationRecognition of viruses by cytoplasmic sensors
Wilkins, C. R., & Gale, M. (2010) · Current Opinion in Immunology · doi:10.1016/j.coi.2009.12.003 · Cited by 428 · see citing works
He, M., Chiang, H.-H., Luo, H., Zheng, Z., Qiao, Q., Wang, L., Tan, M., Ohkubo, R., Mu, W.-C., Zhao, S., et al. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2020.01.009 · Cited by 425 · see citing works
- Authors
- Fernandes-Alnemri, T., Yu, J.-W., Datta, P., Wu, J., & Alnemri, E. S.
- Affiliations
- Thomas Jefferson University (US)
- Corresponding author
- Alnemri, Emad S.
- Venue
- Nature
- Published
- 2009-01-21
- Volume
- 458
- Issue
- 7237
- Pages
- 509-513
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC2862225
- OpenAlex
- W2042288276
- Cited by
- 1,831
- References
- 18
- Citations by year
- 2026: 56 · 2025: 78 · 2024: 96 · 2023: 108 · 2022: 110 · 2021: 101 · 2020: 102 · 2019: 112 · 2018: 114 · 2017: 111 · 2016: 105 · 2015: 109 · 2014: 92 · 2013: 126 · 2012: 100
- FWCI
- 54.95
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- YUHSpace (Yonsei University Medical Library) (submittedVersion, cc-by-nc-nd)
- The Medicine Forum (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (AG14357, R01AG014357)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR-055398, R01AR055398)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- AIM2, cytosolic DNA sensing, inflammasome, pyroptosis, caspase-1, ASC, pyrin domain, innate immunity, macrophages, NF-κB, IL-1β
- MeSH terms
- Animals, Cell Line, Cytoplasm, Cytoskeletal Proteins, DNA, DNA-Binding Proteins, Enzyme Activation, Humans, Inflammation, Nuclear Proteins, Protein Binding, Cell Death, Caspase 1, Apoptosis Regulatory Proteins, Mice, CARD Signaling Adaptor Proteins
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