The Danger Model: A Renewed Sense of Self

Matzinger, Polly

doi:10.1126/science.1071059

Cited by 4,205Immune Response and InflammationT-cell and B-cell ImmunologyArtificial Immune Systems Applications

The Danger Model: A Renewed Sense of Self

Matzinger, Polly·2002·Science

DOI 10.1126/science.1071059

Open this paper in CoChat — free account

Abstract

For over 50 years immunologists have based their thoughts, experiments, and clinical treatments on the idea that the immune system functions by making a distinction between self and nonself. Although this paradigm has often served us well, years of detailed examination have revealed a number of inherent problems. This Viewpoint outlines a model of immunity based on the idea that the immune system is more concerned with entities that do damage than with those that are foreign.

Integrity signals

Registry

Crossref · 10.1126/science.1071059

Cites

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Physiological apoptosis is intrinsically tolerogenic, whereas pathological necrosis is inherently immunogenic and elicits inflammatory reactions.
“The second approach is based on the theory that distinct types of cell death (Box 2) induce different types of immune responses: that physiological cell death (apoptosis) is intrinsically tolerogenic, whereas pathological cell death (necrosis) is inherently immunogenic and elicits inflammatory reactions5.”
From Immunogenic and tolerogenic cell death (2009) · cites this paper as [5]
Danger signals are endogenous signaling molecules that are released in response to 'danger' and activate immune processes to help the organism respond to the adverse event, even in the absence of foreign pathogens.
“Danger signals are endogenous signaling molecules that are released in response to 'danger' and activate immune processes to help the organism respond to the adverse event, even in the absence of foreign pathogens (Matzinger, 2002).”
From Repeated Social Defeat, Neuroinflammation, and Behavior: Monocytes Carry the Signal (2017) · cites this paper as Matzinger, 2002
The inflammasome complex mediates caspase-1 activation.
“A seminal article that identified the inflammasome complex as the mediator of caspase-1activation.”
From Repeated Social Defeat, Neuroinflammation, and Behavior: Monocytes Carry the Signal (2017) · cites this paper as [91]
Pro-caspase-1 is cleaved to the bioactive caspase-1 that cleaves pro-IL-1β to mature IL-1β.
“Pro-caspase-1 is cleaved to the bioactive caspase-1 that cleaves pro-IL-1β to mature IL-1β.”
From Repeated Social Defeat, Neuroinflammation, and Behavior: Monocytes Carry the Signal (2017) · cites this paper as [91]
NLRP3 forms a multiprotein complex with ASC and pro-caspase-1 termed the inflammasome.
“In turn, NLRP3 forms a multiprotein complex with ASC and pro-caspase-1 termed the inflammasome.”
From Repeated Social Defeat, Neuroinflammation, and Behavior: Monocytes Carry the Signal (2017) · cites this paper as [91]

Sorted by citations

Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018.
Galluzzi, L., Vitale, I., Aaronson, S. A., Abrams, J. M., Adam, D., Agostinis, P., Alnemri, E. S., Altucci, L., Amelio, I., Andrews, D. W., et al. (2018) · Cell Death & Differentiation · doi:10.1038/s41418-017-0012-4 · Cited by 6,680 · see citing works
The Inflammasome
Martinon, F., Burns, K., & Tschopp, J. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00599-3 · Cited by 6,066 · see citing works
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 · see citing works
Neutrophils and immunity: challenges and opportunities
Nathan, C. (2006) · Nature reviews. Immunology · doi:10.1038/nri1785 · Cited by 2,971 · see citing works
Points of control in inflammation
Nathan, C. (2002) · Nature · doi:10.1038/nature01320 · Cited by 2,738 · see citing works
The Inflammasomes: Guardians of the Body
Martinon, F., Mayor, A., & Tschopp, J. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132715 · Cited by 2,436 · see citing works
Decoding the Patterns of Self and Nonself by the Innate Immune System
Medzhitov, R., & Janeway, C. A. (2002) · Science · doi:10.1126/science.1068883 · Cited by 2,154 · see citing works
Immunosuppressive networks in the tumour environment and their therapeutic relevance
Zou, W. (2005) · Nature Reviews Cancer · doi:10.1038/nrc1586 · Cited by 2,057 · see citing works
Activation of the NLRP3 inflammasome in dendritic cells induces IL-1β–dependent adaptive immunity against tumors
Ghiringhelli, F., Apetoh, L., Tesniere, A., Aymeric, L., Ma, Y., Ortiz, C., Vermaelen, K., Panaretakis, T., Mignot, G., Ullrich, E., et al. (2009) · Nature Medicine · doi:10.1038/nm.2028 · Cited by 1,898 · see citing works
An ecological and evolutionary perspective on human–microbe mutualism and disease
Dethlefsen, L., McFall-Ngai, M., & Relman, D. A. (2007) · Nature · doi:10.1038/nature06245 · Cited by 1,660 · see citing works
DAMP-sensing receptors in sterile inflammation and inflammatory diseases
Gong, T., Liu, L., Jiang, W., & Zhou, R. (2020) · Nature Reviews Immunology · doi:10.1038/s41577-019-0215-7 · Cited by 1,672 · see citing works
Caspase-dependent immunogenicity of doxorubicin-induced tumor cell death
Casares, N., Pequignot, M. O., Tesniere, A., Ghiringhelli, F., Roux, S., Chaput, N., Schmitt, E., Hamai, A., Hervas-Stubbs, S., Obeid, M., et al. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20050915 · Cited by 1,512 · see citing works
Immunostimulation with chemotherapy in the era of immune checkpoint inhibitors
Galluzzi, L., Humeau, J., Buqué, A., Zitvogel, L., & Kroemer, G. (2020) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-020-0413-z · Cited by 1,349 · see citing works
Immunogenic and tolerogenic cell death
Green, D. R., Ferguson, T., Zitvogel, L., & Kroemer, G. (2009) · Nature Reviews Immunology · doi:10.1038/nri2545 · Cited by 1,176 · see citing works
Type 2 immunity in tissue repair and fibrosis
Gieseck, R. L., Wilson, M. S., & Wynn, T. A. (2018) · Nature Reviews Immunology · doi:10.1038/nri.2017.90 · Cited by 1,055 · see citing works
Cancer cell–autonomous contribution of type I interferon signaling to the efficacy of chemotherapy
Sistigu, A., Yamazaki, T., Vacchelli, E., Chaba, K., Enot, D. P., Adam, J., Vitale, I., Goubar, A., Baracco, E. E., Remédios, C., et al. (2014) · Nature Medicine · doi:10.1038/nm.3708 · Cited by 1,042 · see citing works
Adenosine 5′-triphosphate and adenosine as endogenous signaling molecules in immunity and inflammation
Bours, M. J. L., Swennen, E. L. R., Di Virgilio, F., Cronstein, B. N., & Dagnelie, P. C. (2006) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2005.04.013 · Cited by 1,030 · see citing works
Immune responses to AAV vectors: overcoming barriers to successful gene therapy
Mingozzi, F., & High, K. A. (2013) · Blood · doi:10.1182/blood-2013-01-306647 · Cited by 955 · see citing works
Therapeutic in vivo gene transfer for genetic disease using AAV: Progress and challenges
Mingozzi, F., & High, K. A. (2011) · Nature Reviews Genetics · doi:10.1038/nrg2988 · Cited by 893 · see citing works
International Consensus Statement on Allergy and Rhinology: Rhinosinusitis
Orlandi, R. R., Kingdom, T. T., Hwang, P. H., Smith, T. L., Alt, J. A., Baroody, F. M., Batra, P. S., Bernal‐Sprekelsen, M., Bhattacharyya, N., Chandra, R. K., et al. (2016) · International Forum of Allergy & Rhinology · doi:10.1002/alr.21695 · Cited by 892 · 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
Consensus guidelines for the detection of immunogenic cell death
Kepp, O., Senovilla, L., Vitale, I., Vacchelli, E., Adjemian, S., Agostinis, P., Apetoh, L., Aranda, F., Barnaba, V., Bloy, N., et al. (2014) · OncoImmunology · doi:10.4161/21624011.2014.955691 · Cited by 832 · see citing works
Identification of a dendritic cell receptor that couples sensing of necrosis to immunity
Sancho, D., Joffre, O. P., Keller, A. M., Rogers, N. C., Martínez, D., Hernanz-Falcón, P., Rosewell, I., & Sousa, C. R. E. (2009) · Nature · doi:10.1038/nature07750 · Cited by 750 · see citing works
HMGB1: Endogenous Danger Signaling
Klune, J. R., Dhupar, R., Cardinal, J., Billiar, T. R., & Tsung, A. (2008) · Molecular Medicine · doi:10.2119/2008-00034.klune · Cited by 762 · see citing works
TLR signaling tailors innate immune responses in human microglia and astrocytes
Jack, C. S., Arbour, N., Manusow, J., Montgrain, V., Blain, M., McCrea, E., Shapiro, A., & Antel, J. P. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.7.4320 · Cited by 734 · see citing works
The IL-1-like cytokine IL-33 is inactivated after maturation by caspase-1
Cayrol, C., & Girard, J.-P. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0812690106 · Cited by 707 · see citing works
Hyaluronan Fragments Act as an Endogenous Danger Signal by Engaging TLR2
Scheibner, K. A., Lutz, M. A., Boodoo, S., Fenton, M. J., Powell, J. D., & Horton, M. R. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.2.1272 · Cited by 708 · 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
AAV Vector Immunogenicity in Humans: A Long Journey to Successful Gene Transfer
Costa Verdera, H., Kuranda, K., & Mingozzi, F. (2020) · Molecular Therapy · doi:10.1016/j.ymthe.2019.12.010 · Cited by 641 · see citing works
Induction of Immunological Tolerance by Apoptotic Cells Requires Caspase-Dependent Oxidation of High-Mobility Group Box-1 Protein
Kazama, H., Ricci, J.-E., Herndon, J. M., Hoppe, G., Green, D. R., & Ferguson, T. A. (2008) · Immunity · doi:10.1016/j.immuni.2008.05.013 · Cited by 627 · see citing works
Apoptosis and necroptosis in the liver: a matter of life and death
Schwabe, R. F., & Luedde, T. (2018) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-018-0065-y · Cited by 582 · see citing works
Hyaluronan Fragments Stimulate Endothelial Recognition of Injury through TLR4
Taylor, K. R., Trowbridge, J. M., Rudisill, J. A., Termeer, C. C., Simon, J. C., & Gallo, R. L. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m310859200 · Cited by 545 · see citing works
Triggering the succinate receptor GPR91 on dendritic cells enhances immunity
Rubic, T., Lametschwandtner, G., Jost, S., Hinteregger, S., Kund, J., Carballido-Perrig, N., Schwärzler, C., Junt, T., Voshol, H., Meingassner, J. G., et al. (2008) · Nature Immunology · doi:10.1038/ni.1657 · Cited by 525 · see citing works
An official European Respiratory Society statement on physical activity in COPD
Watz, H., Pitta, F., Rochester, C. L., Garcia-Aymerich, J., ZuWallack, R., Troosters, T., Vaes, A. W., Puhan, M. A., Jehn, M., Polkey, M. I., et al. (2014) · European Respiratory Journal · doi:10.1183/09031936.00046814 · Cited by 526 · see citing works
Self- and nonself-recognition by C-type lectins on dendritic cells
Geijtenbeek, T. B. H., van Vliet, S. J., Engering, A., 't Hart, B. A., & van Kooyk, Y. (2004) · Annual Review of Immunology · doi:10.1146/annurev.immunol.22.012703.104558 · Cited by 503 · see citing works
Liaisons dangereuses: P2X7 and the inflammasome
Di Virgilio, F. (2007) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2007.07.002 · Cited by 493 · see citing works
Homeostasis-altering molecular processes as mechanisms of inflammasome activation
Liston, A., & Masters, S. L. (2017) · Nature Reviews Immunology · doi:10.1038/nri.2016.151 · Cited by 459 · see citing works
Recent insights into the immunopathogenesis of psoriasis provide new therapeutic opportunities
Nickoloff, B. J., & Nestle, F. O. (2004) · Journal of Clinical Investigation · doi:10.1172/jci200422147 · Cited by 544 · see citing works
Dying cells actively regulate adaptive immune responses
Yatim, N., Cullen, S., & Albert, M. L. (2017) · Nature Reviews Immunology · doi:10.1038/nri.2017.9 · Cited by 442 · see citing works
Activation of the IL-1β-Processing Inflammasome Is Involved in Contact Hypersensitivity
Watanabe, H., Gaide, O., Pétrilli, V., Martinon, F., Contassot, E., Roques, S., Kummer, J. A., Tschopp, J., & French, L. E. (2007) · Journal of Investigative Dermatology · doi:10.1038/sj.jid.5700819 · Cited by 416 · see citing works
Uric Acid Is a Danger Signal Activating NALP3 Inflammasome in Lung Injury Inflammation and Fibrosis
Gasse, P., Riteau, N., Charron, S., Girre, S., Fick, L., Pétrilli, V., Tschopp, J., Lagente, V., Quesniaux, V. F. J., Ryffel, B., et al. (2009) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200808-1274oc · Cited by 410 · see citing works
Neuromodulation by the immune system: a focus on cytokines
Salvador, A. F., de Lima, K. A., & Kipnis, J. (2021) · Nature Reviews Immunology · doi:10.1038/s41577-021-00508-z · Cited by 389 · see citing works
Parainflammation, Chronic Inflammation and Age-Related Macular Degeneration
Chen, M., & Xu, H. (2015) · Journal of Leukocyte Biology · doi:10.1189/jlb.3ri0615-239r · Cited by 381 · see citing works
NLRs at the intersection of cell death and immunity
Ting, J. P.-Y., Willingham, S. B., & Bergstralh, D. T. (2008) · Nature Reviews Immunology · doi:10.1038/nri2296 · Cited by 371 · see citing works
Dealing with danger in the CNS: the response of the immune system to injury
Gadani, S. P., Walsh, J. T., Lukens, J. R., & Kipnis, J. (2015) · Neuron · doi:10.1016/j.neuron.2015.05.019 · Cited by 342 · see citing works
Gut-origin sepsis: evolution of a concept
Deitch, E. A. (2012) · The Surgeon · doi:10.1016/j.surge.2012.03.003 · Cited by 359 · see citing works
Vulvovaginal Candidiasis: A Current Understanding and Burning Questions
Willems, H. M. E., Ahmed, S. S., Liu, J., Xu, Z., & Peters, B. M. (2020) · Journal of Fungi · doi:10.3390/jof6010027 · Cited by 357 · see citing works
Metal Drugs and the Anticancer Immune Response
Englinger, B., Pirker, C., Heffeter, P., Terenzi, A., Kowol, C. R., Keppler, B. K., & Berger, W. (2019) · Chemical Reviews · doi:10.1021/acs.chemrev.8b00396 · Cited by 355 · see citing works
Repeated Social Defeat, Neuroinflammation, and Behavior: Monocytes Carry the Signal
Weber, M. D., Godbout, J. P., & Sheridan, J. F. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2016.102 · Cited by 283 · see citing works
Letter to the Glyco-Forum: Since there are PAMPs and DAMPs, there must be SAMPs? Glycan "self-associated molecular patterns" dampen innate immunity, but pathogens can mimic them
Varki, A. (2011) · Glycobiology · doi:10.1093/glycob/cwr087 · Cited by 263 · see citing works
Transient TLR Activation Restores Inflammatory Response and Ability To Control Pulmonary Bacterial Infection in Germfree Mice
Fagundes, C. T., Amaral, F. A., Vieira, A. T., Soares, A. C., Pinho, V., Nicoli, J. R., Vieira, L. Q., Teixeira, M. M., & Souza, D. G. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1101682 · Cited by 244 · see citing works
CX3CL1 reduces neurotoxicity and microglial activation in a rat model of Parkinson’s disease
Pabon, M. M., Bachstetter, A. D., Hudson, C. E., Gemma, C., & Bickford, P. C. (2011) · Journal of Neuroinflammation · doi:10.1186/1742-2094-8-9 · Cited by 241 · see citing works
Immune checkpoint inhibitor–associated myocarditis: manifestations and mechanisms
Moslehi, J., Lichtman, A. H., Sharpe, A. H., Galluzzi, L., & Kitsis, R. N. (2021) · Journal of Clinical Investigation · doi:10.1172/jci145186 · Cited by 237 · see citing works
Stress sounds the alarmin: The role of the danger-associated molecular pattern HMGB1 in stress-induced neuroinflammatory priming
Frank, M. G., Weber, M. D., Watkins, L. R., & Maier, S. F. (2015) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2015.03.010 · Cited by 237 · see citing works
Ubiquitin in the immune system
Zinngrebe, J., Montinaro, A., Peltzer, N., & Walczak, H. (2014) · The EMBO Reports · doi:10.1002/embr.201338025 · Cited by 227 · see citing works
NALP Inflammasomes: a central role in innate immunity
Martinon, F., Gaide, O., Pétrilli, V., Mayor, A., & Tschopp, J. (2007) · Seminars in Immunopathology · doi:10.1007/s00281-007-0079-y · Cited by 218 · see citing works
Stress Induces the Danger-Associated Molecular Pattern HMGB-1 in the Hippocampus of Male Sprague Dawley Rats: A Priming Stimulus of Microglia and the NLRP3 Inflammasome
Weber, M. D., Frank, M. G., Tracey, K. J., Watkins, L. R., & Maier, S. F. (2015) · The Journal of Neuroscience · doi:10.1523/jneurosci.3561-14.2015 · Cited by 215 · see citing works
Overcoming the Host Immune Response to Adeno-Associated Virus Gene Delivery Vectors: The Race Between Clearance, Tolerance, Neutralization, and Escape
Mingozzi, F., & High, K. A. (2017) · Annual Review of Virology · doi:10.1146/annurev-virology-101416-041936 · Cited by 206 · see citing works
The community of the self
Buchman, T. G. (2002) · Nature · doi:10.1038/nature01260 · Cited by 207 · see citing works
Ecto‐calreticulin in immunogenic chemotherapy
Obeid, M., Tesniere, A., Panaretakis, T., Tufi, R., Joza, N., Van Endert, P., Ghiringhelli, F., Apetoh, L., Chaput, N., Flament, C., et al. (2007) · Immunological Reviews · doi:10.1111/j.1600-065x.2007.00567.x · Cited by 202 · see citing works
The untold story of IFN-γ in cancer biology
Kursunel, M. A., & Esendagli, G. (2016) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2016.07.005 · Cited by 192 · see citing works
Neuroimmune signaling: a key component of alcohol abuse
Mayfield, J., Ferguson, L., & Harris, R. A. (2013) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2013.01.024 · Cited by 193 · see citing works
High‐mobility group box‐1 in sterile inflammation
Tsung, A., Tohme, S., & Billiar, T. R. (2014) · Journal of Internal Medicine · doi:10.1111/joim.12276 · Cited by 187 · see citing works
Extracellular ATP induces oscillations of intracellular Ca <sup>2+</sup> and membrane potential and promotes transcription of IL-6 in macrophages
Hanley, P. J., Musset, B., Renigunta, V., Limberg, S. H., Dalpke, A. H., Sus, R., Heeg, K. M., Preisig-Müller, R., & Daut, J. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0400733101 · Cited by 168 · see citing works
The Biological Role of Inflammation in Atherosclerosis
Wong, B. W., Meredith, A., Lin, D., & McManus, B. M. (2012) · Canadian Journal of Cardiology · doi:10.1016/j.cjca.2012.06.023 · Cited by 168 · see citing works
Stress-induced glucocorticoids as a neuroendocrine alarm signal of danger
Frank, M. G., Watkins, L. R., & Maier, S. F. (2013) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2013.02.004 · Cited by 160 · see citing works
Transcriptomic Analysis of Vulvovaginal Candidiasis Identifies a Role for the NLRP3 Inflammasome
Bruno, V. M., Shetty, A. C., Yano, J., Fidel, P. L., Noverr, M. C., & Peters, B. M. (2015) · mBio · doi:10.1128/mbio.00182-15 · Cited by 155 · see citing works
Hemorrhagic Shock Activation of NLRP3 Inflammasome in Lung Endothelial Cells
Xiang, M., Shi, X., Li, Y., Xu, J., Yin, L., Xiao, G., Scott, M. J., Billiar, T. R., Wilson, M. A., & Fan, J. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1102093 · Cited by 155 · see citing works
Role of the IL-6 classic- and trans-signaling pathways in corneal sterile inflammation and wound healing
Ebihara, N., Matsuda, A., Nakamura, S., Matsuda, H., & Murakami, A. (2011) · Investigative Opthalmology & Visual Science · doi:10.1167/iovs.11-7956 · Cited by 147 · see citing works
DAMPs, ageing, and cancer: The ‘DAMP Hypothesis’
Huang, J., Xie, Y., Sun, X., Zeh, H. J., Kang, R., Lotze, M. T., & Tang, D. (2015) · Ageing Research Reviews · doi:10.1016/j.arr.2014.10.004 · Cited by 144 · see citing works
Complement in removal of the dead – balancing inflammation
Martin, M., & Blom, A. M. (2016) · Immunological Reviews · doi:10.1111/imr.12462 · Cited by 130 · see citing works
Mitochondrial damage-associated molecular patterns and vascular function
Wenceslau, C. F., McCarthy, C. G., Szasz, T., Spitler, K., Goulopoulou, S., Webb, R. C., & Working Group on DAMPs in Cardiovascular Disease (2014) · European Heart Journal · doi:10.1093/eurheartj/ehu047 · Cited by 135 · see citing works
Toll‐like receptors and pregnancy: Trophoblast as modulators of the immune response
Koga, K., Aldo, P. B., & Mor, G. (2009) · Journal of Obstetrics and Gynaecology Research · doi:10.1111/j.1447-0756.2008.00963.x · Cited by 130 · see citing works
Pathogen response-like recruitment and activation of neutrophils by sterile immunogenic dying cells drives neutrophil-mediated residual cell killing
Garg, A. D., Vandenberk, L., Fang, S., Fasche, T., Van Eygen, S., Maes, J., Van Woensel, M., Koks, C., Vanthillo, N., Graf, N., et al. (2017) · Cell Death & Differentiation · doi:10.1038/cdd.2017.15 · Cited by 120 · see citing works
Hsp70: Anti-apoptotic and Tumorigenic Protein
Rérole, A.-L., Jego, G., & Garrido, C. (2011) · Methods in Molecular Biology · doi:10.1007/978-1-61779-295-3_16 · Cited by 118 · see citing works
Autoimmune Aspects of Type 2 Diabetes Mellitus - A Mini-Review
Itariu, B. K., & Stulnig, T. M. (2014) · Gerontology · doi:10.1159/000356747 · Cited by 107 · see citing works
Trial Watch: experimental TLR7/TLR8 agonists for oncological indications
Frega, G., Wu, Q., Le Naour, J., Vacchelli, E., Galluzzi, L., Kroemer, G., & Kepp, O. (2020) · OncoImmunology · doi:10.1080/2162402x.2020.1796002 · Cited by 108 · see citing works
IL-1α Is a DNA Damage Sensor Linking Genotoxic Stress Signaling to Sterile Inflammation and Innate Immunity
Cohen, I., Rider, P., Vornov, E., Tomas, M., Tudor, C., Wegner, M., Brondani, L., Freudenberg, M., Mittler, G., Ferrando-May, E., et al. (2015) · Scientific Reports · doi:10.1038/srep14756 · Cited by 98 · see citing works
Trauma hemorrhagic shock-induced lung injury involves a gut-lymph-induced TLR4 pathway in mice
Reino, D. C., Pisarenko, V., Palange, D., Doucet, D., Bonitz, R. P., Lu, Q., Colorado, I., Sheth, S. U., Chandler, B., Kannan, K. B., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0014829 · Cited by 97 · see citing works
Resolution-associated molecular patterns (RAMP): RAMParts defending immunological homeostasis?
Shields, A. M., Panayi, G. S., & Corrigall, V. M. (2011) · Clinical and Experimental Immunology · doi:10.1111/j.1365-2249.2011.04433.x · Cited by 90 · see citing works
Immune-mediated drug-induced liver injury: immunogenetics and experimental models
Gerussi, A., Natalini, A., Antonangeli, F., Mancuso, C., Agostinetto, E., Barisani, D., Di Rosa, F., Andrade, R., & Invernizzi, P. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22094557 · Cited by 87 · see citing works
Cross-presentation of caspase-cleaved apoptotic self antigens in HIV infection
Rawson, P. M., Molette, C., Videtta, M., Altieri, L., Franceschini, D., Donato, T., Finocchi, L., Propato, A., Paroli, M., Meloni, F., et al. (2007) · Nature Medicine · doi:10.1038/nm1679 · Cited by 86 · see citing works
Integrated evolutionary, immunological, and neuroendocrine framework for the pathogenesis of chronic disabling inflammatory diseases
Straub, R. H., & Besedovsky, H. O. (2003) · The FASEB Journal · doi:10.1096/fj.03-0433hyp · Cited by 85 · see citing works
Amyloid β: one of three danger‐associated molecules that are secondary inducers of the proinflammatory cytokines that mediate <scp>A</scp>lzheimer's disease
Clark, I. A., & Vissel, B. (2015) · British Journal of Pharmacology · doi:10.1111/bph.13181 · Cited by 84 · see citing works
Liver induced transgene tolerance with AAV vectors
Keeler, G. D., Markusic, D. M., & Hoffman, B. E. (2019) · Cellular Immunology · doi:10.1016/j.cellimm.2017.12.002 · Cited by 81 · see citing works
Acute Brain Injury Triggers MyD88-Dependent, TLR2/4-Independent Inflammatory Responses
Koedel, U., Merbt, U. M., Schmidt, C., Angele, B., Popp, B., Wagner, H., Pfister, H.-W., & Kirschning, C. J. (2007) · The American Journal of Pathology · doi:10.2353/ajpath.2007.060821 · Cited by 78 · see citing works
Exercise and inflammation
Febbraio, M. A. (2007) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00414.2007 · Cited by 70 · see citing works
DNase II activated by the mitochondrial apoptotic pathway regulates RIP1-dependent non-apoptotic hepatocyte death via the TLR9/IFN-β signaling pathway
Saito, Y., Hikita, H., Nozaki, Y., Kai, Y., Makino, Y., Nakabori, T., Tanaka, S., Yamada, R., Shigekawa, M., Kodama, T., et al. (2019) · Cell Death & Differentiation · doi:10.1038/s41418-018-0131-6 · Cited by 66 · see citing works
Preeclampsia: a view through the danger model
Bonney, E. A. (2007) · Journal of Reproductive Immunology · doi:10.1016/j.jri.2007.03.006 · Cited by 53 · see citing works
Personalizing neoadjuvant immune-checkpoint inhibition in patients with melanoma
Lucas, M. W., Versluis, J. M., Rozeman, E. A., & Blank, C. U. (2023) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-023-00760-3 · Cited by 50 · see citing works
Frank A. Beach Award: Programming of neuroendocrine function by early-life experience: A critical role for the immune system
Bilbo, S. D. (2013) · Hormones and Behavior · doi:10.1016/j.yhbeh.2013.02.017 · Cited by 46 · see citing works
Separating Lentiviral Vector Injection and Induction of Gene Expression in Time, Does Not Prevent an Immune Response to rtTA in Rats
Markusic, D. M., de Waart, D. R., & Seppen, J. (2010) · PLoS ONE · doi:10.1371/journal.pone.0009974 · Cited by 22 · see citing works
Emerging Concepts for the Pathogenesis of Chronic Disabling Inflammatory Diseases: Neuroendocrine-immune Interactions and Evolutionary Biology
STRAUB, R. H., DEL REY, A., & BESEDOVSKY, H. O. (2007) · Psychoneuroimmunology · doi:10.1016/b978-012088576-3/50014-9 · Cited by 14 · see citing works
Taurine lowers inflammaging by regulating the NLRP3 inflammasome in macrophages
Guan, C., Ryu, S., Dong, M., Zhu, Y., Maeda, R., Youm, Y.-H., Mohanty, S., Kim, H.-H., Orliaguet, L., Dlugos, T., et al. (2026) · Cell · doi:10.1016/j.cell.2026.09.061

Authors: Matzinger, P.
Affiliations: National Institutes of Health (US)
Corresponding author: Matzinger, Polly
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 2002-04-12
Volume: 296
Issue: 5566
Pages: 301-305
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.1071059
OpenAlex: W2145736817
Cited by: 4,205
References: 0
Citations by year: 2026: 73 · 2025: 52 · 2024: 87 · 2023: 90 · 2022: 119 · 2021: 193 · 2020: 141 · 2019: 148 · 2018: 167 · 2017: 179 · 2016: 191 · 2015: 224 · 2014: 220 · 2013: 224 · 2012: 251
FWCI: 48.58
Type: journal article
Language: en
Open access: closed
Locations: Science (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Physical Sciences › Engineering › Biomedical Engineering › Artificial Immune Systems Applications
Keywords: danger model, immune function, damage-associated molecular patterns, innate immunity, immune tolerance
MeSH terms: Animals, Antigen-Presenting Cells, B-Lymphocytes, Fetus, Humans, Immune System, Immunity, Infections, Neoplasms, Receptors, Cell Surface, Receptors, Immunologic, T-Lymphocytes, Autoimmunity, Self Tolerance, Models, Immunological, Transplantation Tolerance

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

The Danger Model: A Renewed Sense of Self

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Cited by

Record

About these checks