Cited by 371Inflammasome and immune disordersImmune Response and InflammationCell death mechanisms and regulation

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NLRs at the intersection of cell death and immunity

Ting, Jenny P.-Y., Willingham, Stephen B., Bergstralh, Daniel T.·2008·Nature Reviews Immunology

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Abstract

Inflammation is a crucial element of the host response to cellular insult. Pathogen-induced inflammation includes a molecular pathway which proceeds through activation of the protease caspase-1 to the release of the inflammatory cytokines interleukin-1 (IL-1) and IL-18. Importantly, pathogens may also induce forms of cell death that have inherently pro-inflammatory features. Here, we review recent evidence demonstrating that NLR (nucleotide-binding domain, leucine-rich repeat containing) family proteins serve as a common component of both caspase-1-activated apoptotic pathways and caspase-independent necrotic pathways. Parallels are drawn between NLR protein function and the activity of structurally similar proteins involved in cell death: the apoptotic mediator APAF1 (apoptotic-protease-activating factor 1) and the plant disease resistance NBS-LRR (nucleotide-binding site leucine-rich repeats) proteins.

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Innate immune recognition
Janeway, C. A., & Medzhitov, R. (2002) · Annual Review of Immunology · doi:10.1146/annurev.immunol.20.083001.084359 · Cited by 8,394
The Inflammasome
Martinon, F., Burns, K., & Tschopp, J. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00599-3 · Cited by 6,066
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
Biologic basis for interleukin-1 in disease.
Dinarello, C. (1996) · Blood · doi:10.1182/blood.v87.6.2095.bloodjournal8762095 · Cited by 4,344
The Danger Model: A Renewed Sense of Self
Matzinger, P. (2002) · Science · doi:10.1126/science.1071059 · Cited by 4,205
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Manuscript Preparation
Editorial Office (1997) · Obesity Surgery · doi:10.1381/096089297765555359 · Cited by 3,941
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Hayashi, F., Smith, K. D., Ozinsky, A., Hawn, T. R., Yi, E. C., Goodlett, D. R., Eng, J. K., Akira, S., Underhill, D. M., & Aderem, A. A. (2001) · Nature · doi:10.1038/35074106 · Cited by 3,605

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Su, X., Zhao, S., & Song, Y. (2022) · Scientific Reports · doi:10.1038/s41598-022-19398-9 · Cited by 8
Excitotoxicity and Wallerian degeneration as a processes related to cell death in nervous system.
Działo, J., Tokarz–Deptuła, B., & Deptuła, W. (2013) · PubMed · doi:10.4449/aib.v151i2.1471 · Cited by 8
“Their characteristic features include the involvement of Nod like receptors (NLR) in their induction, and formation of protein complexes termed inflammasomes (bergsbaken et al., 2009; Ting et al., 2008).”
Background
Novel Innate Immune Genes Regulating the Macrophage Response to Gram Positive Bacteria
Alper, S., Warg, L. A., Arras, L. D., Flatley, B. R., Davidson, E., Adams, J., Smith, K. P., Wohlford-Lenane, C., McCray, P. B., Pedersen, B. S., et al. (2016) · Genetics · doi:10.1534/genetics.115.185314 · Cited by 8
“Ting, J. P., S. B. Willingham, and D. T. Bergstralh, 2008 NLRs at the intersection of cell death and immunity.”
Background
Cell Death in Cardiovascular Disease
Bennett, M. R. (2011) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.111.239954 · Cited by 8
Implant Debris: Clinical Data and Relevance
Hallab, N. J., & Jacobs, J. J. (2011) · Comprehensive Biomaterials · doi:10.1016/b978-0-08-055294-1.00207-5 · Cited by 8
Identification of Mutations in the PYRIN-Containing NLR Genes (NLRP) in Head and Neck Squamous Cell Carcinoma
Lei, Y. L., Lui, V. W. Y., Grandis, J. R., & Egloff, A. M. (2014) · PLoS ONE · doi:10.1371/journal.pone.0085619 · Cited by 7
“A variety of NLR-mediated signaling pathways convey meticulous regulatory mechanisms in cell death [11], inflammation [9,10,12], autophagy [13–16], and more recently carcinogenesis [17–24].”
Background
Gene expression and involvement of signaling pathways during host–pathogen interplay in Orientia tsutsugamushi infection
Panda, S., Swain, S. K., Sahu, B. P., & Sarangi, R. (2022) · 3 Biotech · doi:10.1007/s13205-022-03239-7 · Cited by 9
“The pathogen recognition receptors (PRR), macrophages, dendritic cells, and neutrophils sense the invading pathogens to activate the natural immune response and promote adaptive immune responses (Ting et al. 2008).”
Background
Infection process in resistant and susceptible maize (Zea mays L.) genotypes to Cercospora zeae-maydis (type II)
Lyimo, H. J. F., Pratt, R. C., & Mnyuku, R. S. O. W. (2013) · Plant Protection Science · doi:10.17221/57/2011-pps · Cited by 7
Overview of the immunomodulatory role of bacterial probiotic-derived peptidoglycan: from molecular insights to therapeutic application
Allela, O. Q. B., Shareef, A., Sameer, H. N., Yaseen, A., Athab, Z. H., & Adil, M. (2026) · Frontiers in Microbiology · doi:10.3389/fmicb.2026.1761985 · Cited by 6
Platelet’s plea to Immunologists: Please do not forget me
Kumar, V., & Stewart, J. H. (2024) · International Immunopharmacology · doi:10.1016/j.intimp.2024.113599 · Cited by 7
Identification of DMSA-Coated Fe3O4 Nanoparticles Induced-Apoptosis Response Genes in Human Monocytes by cDNA Microarrays
Liu, Y. X., Huang, J. Y., Wang, D., & Wang, J. K. (2013) · Advanced materials research · doi:10.4028/www.scientific.net/amr.749.377 · Cited by 6
Lung epithelial cells in the defense against tuberculosis: an essential neglected activity
Jacobo-Delgado, Y. M., González-Muñiz, O. E., Rivas-Santiago, C., & Rivas-Santiago, B. T. (2025) · Microbial Pathogenesis · doi:10.1016/j.micpath.2025.107984 · Cited by 6
Altered Inflammatory Mediators in Fibromyalgia
García, J. J., Gil, J. C., Olea, A. H., & Gómez-Galán, R. (2017) · Journal of Ancient Diseases & Preventive Remedies · doi:10.4172/2329-8731.1000215 · Cited by 5
“The active form of caspase-1 also has the ability to induce the release of IL-1α and HMGB-1, and initiate a lytic form of cell death called pyroptosis, a way of inflammatory lytic cell death [85-88].”
Background
NOD2 and reproduction-associated NOD-like receptors have been lost during the evolution of pangolins
Salova, M., Sipos, W., Tschachler, E., & Eckhart, L. (2021) · Immunogenetics · doi:10.1007/s00251-021-01230-9 · Cited by 5
Characterization of Novel Piperidine-Based Inhibitor of Cathepsin B-Dependent Bacterial Toxins and Viruses
Hartmann, S., Cruz, R. L., Alameh, S., Ho, C.-L. C., Rabideau, A. E., Pentelute, B. L., Bradley, K. A., & Martchenko, M. (2018) · ACS Infectious Diseases · doi:10.1021/acsinfecdis.8b00053 · Cited by 7
Cytokines and the Innate Immune Response at the Materno-Fetal Interface
Aled, H., & Catherine, A. (2012) · InTech eBooks · doi:10.5772/33219 · Cited by 4
Genetic variations of mitochondrial antiviral signaling gene (MAVS) in domestic chickens
Yu, D., Xu, L., Peng, L., Chen, S.-Y., Liu, Y., & Yao, Y. (2014) · Gene · doi:10.1016/j.gene.2014.05.029 · Cited by 5
“The RLRs family members are conserved among vertebrates and contained three members: RIGI, MDA5 (melanoma differentiation-associated gene 5) and LGP2 (laboratory of genetics and physiology 2) (Kawai and Akira, 2007; Ting et al., 2008; Yoneyama and Fujita, 2008).”
Background
Editorial: Synergism between NOD-like receptors and Toll-like receptors in human B lymphocytes
O'Neill, L. A. J. (2011) · Journal of Leukocyte Biology · doi:10.1189/jlb.0910521 · Cited by 5
Bone Biology of Implant Failure
Moran, M. M., Ross, R. D., Virdi, A. S., Hallab, N. J., & Sumner, D. R. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-801238-3.11206-1 · Cited by 5
Polysaccharides derived from Rosa rugosa cv. Plena ameliorate colorectal cancer by regulating intestinal microbiota composition and lipid metabolism pathway
Dai, C.-Y., Zheng, X., Zhu, J., Zhang, H., Jin, J., Pang, X., Li, X., & Xie, Y. (2025) · npj Science of Food · doi:10.1038/s41538-025-00544-2 · Cited by 4
“In humans, NLR are a family of intracellular pattern recognition receptors that play a crucial role in innate immunity 47 .”
Host Molecular Defense Mechanisms Against Chlamydophila pneumoniae and Genetic Studies of Immune-Response-Related Genes in Asthma
Tamari, M., Harada, M., Hirota, T., & Nakamura, Y. (2009) · Recent Patents on Inflammation & Allergy Drug Discovery · doi:10.2174/187221309787158380 · Cited by 4
“Nucleotide-binding oligomerization domain 1 (NOD1) is an intracellular protein that mediates host recognition of intracellular bacteria [60].”
BackgroundInfluential
7.8 Implant Debris: Clinical Data and Relevance ☆
Hallab, N. J., & Jacobs, J. J. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-803581-8.10177-8 · Cited by 4
Non‐canonical effects of anthrax toxins on haematopoiesis: implications for vaccine development
Liu, K., Wong, E. W., Schutzer, S. E., Connell, N. D., Upadhyay, A. K., Bryan, M., & Rameshwar, P. (2008) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2008.00477.x · Cited by 4
“anthracis and other bacterial agents have been linked to macrophage death involving caspase-1 [33], this mediator might be involved as a secondary mechanism in macrophages.”
Background
miR15a regulates NLRP3 inflammasome proteins in the retinal vasculature
Curtiss, E., Liu, L., & Steinle, J. J. (2018) · Experimental Eye Research · doi:10.1016/j.exer.2018.07.005 · Cited by 4
“IL-1β is also released following inflammasome formation, resulting from the cleavage of pro-caspase 1 into caspase 1 (Schroder and Tschopp, 2010; Ting et al., 2008).”
Influential
Editorial: Systemic Lupus Erythematosus: Death by Fire and ICE?
Reeves, W. H. (2013) · Arthritis & Rheumatology · doi:10.1002/art.38224 · Cited by 4
“There is considerable evidence that the NLR proteins are a crucial link between innate immunity and cell death signaling (7).”
Background
Pyronecrosis
Khalili, M., & Radosevich, J. A. (2018) · Wiley eBooks · doi:10.1002/9781119432463.ch12 · Cited by 3
Genetic variations in NLRP1 and Glutathione S-Transferase are associated with Generalized Vitiligo of Phlegmatic Clinical Phenotypes in Unani Medicine Philosophy of South Indian Population
Chakraborty, A., Pallapolu, P., Thulasamma, S., Kuna, L., Ghali, S. K., Jamil, K., Javed, G., & Kazmi, M. H. (2022) · Research Journal of Pharmacy and Technology · doi:10.52711/0974-360x.2022.00369 · Cited by 3
p38MAPK guards the integrity of endosomal compartments through regulating necrotic death
Yao, J., Atasheva, S., Toy, R., Blanchard, E. L., Santangelo, P. J., Roy, K., Mocarski, E. S., & Shayakhmetov, D. M. (2022) · Scientific Reports · doi:10.1038/s41598-022-20786-4 · Cited by 3
Mycobacterium tuberculosis Central Metabolism Is Key Regulator of Macrophage Pyroptosis and Host Immunity
Maxson, M. E., Das, L., Goldberg, M. F., Porcelli, S. A., Chan, J., & Jacobs, W. R. (2023) · Pathogens · doi:10.3390/pathogens12091109 · Cited by 3
“Pyroptosis involves the activation of caspase-1 by the recognition of intracellular danger signals by Nod-like-receptors, culminating in the secretion of IL-1 β and caspase-1-dependent cell death [37,46,47].”
Background
The NLRP1 Emerges as a Promising Therapeutic Target and Prognostic Biomarker Across Multiple Cancer Types: A Comprehensive Pan‐Cancer Analysis
Habibipour, L., Sadeghi, M., Raghibi, A., Sanadgol, N., Khorasani, A. M., & Mousavi, P. (2025) · Cancer Medicine · doi:10.1002/cam4.70836 · Cited by 3
[Simple and useful evaluation of motor difficulty in childhood (9-12 years old children ) by interview score on motor skills and soft neurological signs--aim for the diagnosis of developmental coordination disorder].
Kashiwagi, M., & Suzuki, S. (2009) · PubMed · Cited by 3
Pathogen Sensing: Toll-Like Receptors and NODs (Innate Immunity)
Chandler, C. E., Harberts, E. M., & Ernst, R. K. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-809633-8.90775-1 · Cited by 3

Authors: Ting, J. P.-Y., Willingham, S. B., & Bergstralh, D. T.
Affiliations: University of North Carolina at Chapel Hill (US)
Corresponding author: Ting, Jenny P.-Y.
ORCID: Ting, Jenny P.-Y.
Venue: Nature Reviews Immunology
Publisher: Springer Science and Business Media LLC
Published: 2008-05
Volume: 8
Issue: 5
Pages: 372-379
ISSN: 1474-1733 (ISSN-L)
1474-1741
DOI: 10.1038/nri2296
OpenAlex: W2050870561
Cited by: 371
References: 145
Citations by year: 2026: 5 · 2025: 9 · 2024: 7 · 2023: 8 · 2022: 10 · 2021: 14 · 2020: 10 · 2019: 19 · 2018: 18 · 2017: 18 · 2016: 17 · 2015: 19 · 2014: 22 · 2013: 27 · 2012: 36
FWCI: 3.40
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature reviews. Immunology (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Keywords: NLR proteins, cell death, pyroptosis, caspase-1, apoptosis, necrosis, inflammation, interleukin-1, IL-18, Apaf-1, NBS-LRR proteins, plant disease resistance, host-pathogen interaction
MeSH terms: NLR Proteins, Leucine-Rich Repeat Proteins, Animals, Communicable Diseases, Humans, Interleukin-1, Necrosis, Proteins, Tumor Necrosis Factor-alpha, Apoptosis, Caspase 1, HMGB1 Protein, Intracellular Signaling Peptides and Proteins, Adaptor Proteins, Signal Transducing, Apoptosis Regulatory Proteins, Apoptotic Protease-Activating Factor 1

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