Inflammasomes are multiprotein innate immune complexes that regulate caspase-dependent inflammation and cell death. Pattern recognition receptors, such as nucleotide-binding oligomerization domain (NOD)-like receptors and absent in melanoma 2 (AIM2)-like receptors, sense danger signals or cellular events to activate canonical inflammasomes, resulting in caspase 1 activation, pyroptosis and the secretion of IL-1β and IL-18. Non-canonical inflammasomes can be activated by intracellular lipopolysaccharides, toxins and some cell signalling pathways. These inflammasomes regulate the activation of alternative caspases (caspase 4, caspase 5, caspase 11 and caspase 8) that lead to pyroptosis, apoptosis and the regulation of other cellular pathways. Many inflammasome-related genes and proteins have been implicated in animal models of kidney disease. In particular, the NLRP3 (NOD-, LRR- and pyrin domain-containing 3) inflammasome has been shown to contribute to a wide range of acute and chronic microbial and non-microbial kidney diseases via canonical and non-canonical mechanisms that regulate inflammation, pyroptosis, apoptosis and fibrosis. In patients with chronic kidney disease, immunomodulation therapies targeting IL-1β such as canakinumab have been shown to prevent cardiovascular events. Moreover, findings in experimental models of kidney disease suggest that small-molecule inhibitors targeting NLRP3 and other inflammasome components are promising therapeutic agents.
Canonical inflammasomes are multiprotein complexes that consist of pattern recognition receptors (PRRs), the adaptor protein apoptosis-associated speck-like protein containing a CARD (ASC) and caspase 1.
Canonical inflammasomes regulate activation of caspase 1, which results in the maturation and secretion of cytokines such as IL-1β and IL-18 and the cleavage of gasdermin D (GSDMD), which drives pyroptosis.
Non-canonical inflammasomes activate alternative caspases such as caspase 8, caspase 4, caspase 5 and caspase 11, which drive cell death and regulate canonical inflammasome complex assembly.
The NLRP3 (NOD-, LRR- and pyrin domain-containing 3) inflammasome is activated by danger-associated molecular patterns including extracellular ATP; the absent in melanoma 2 (AIM2) inflammasome is activated by double-stranded DNA.
Inflammasome-forming PRRs and related proteins have been implicated in a variety of kidney diseases, including acute kidney injury, chronic kidney disease and diabetic kidney disease, via canonical and non-canonical pathways.
Novel inflammasome-targeting agents, including an IL-1β monoclonal antibody, caspase 1 inhibitors and NLRP3 inhibitors, have shown promising effects in experimental models and may provide new therapeutic strategies for kidney disease.
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Lamkanfi, M. & Dixit, V. M. Mechanisms and functions of inflammasomes. Cell 157, 1013–1022 (2014).
Rathinam, V. A. K. & Chan, F. K. Inflammasome, inflammation, and tissue homeostasis. Trends Mol. Med. 24, 304–318 (2018).
Soares, J. L. S. et al. Gain-of-function variants in NLRP1 protect against the development of diabetic kidney disease: NLRP1 inflammasome role in metabolic stress sensing? Clin. Immunol. 187, 46–49 (2018).
Cheng, C. H., Lee, Y. S., Chang, C. J., Lin, J. C. & Lin, T. Y. Genetic polymorphisms in inflammasome-dependent innate immunity among pediatric patients with severe renal parenchymal infections. PLOS ONE 10, e0140128 (2015).
He, W. T. et al. Gasdermin D is an executor of pyroptosis and required for interleukin-1β secretion. Cell Res. 25, 1285–1298 (2015).
Martinon, F., Burns, K. & Tschopp, J. The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-1β. Mol. Cell 10, 417–426 (2002).
Minkiewicz, J., de Rivero Vaccari, J. P. & Keane, R. W. Human astrocytes express a novel NLRP2 inflammasome. Glia 61, 1113–1121 (2013).
Martinon, F., Petrilli, V., Mayor, A., Tardivel, A. & Tschopp, J. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature 440, 237–241 (2006).
Levy, M. et al. Microbiota-modulated metabolites shape the intestinal microenvironment by regulating NLRP6 inflammasome signaling. Cell 163, 1428–1443 (2015).
Hara, H. et al. The NLRP6 inflammasome recognizes lipoteichoic acid and regulates gram-positive pathogen infection. Cell 175, 1651–1664 (2018).
Broz, P. et al. Redundant roles for inflammasome receptors NLRP3 and NLRC4 in host defense against Salmonella. J. Exp. Med. 207, 1745–1755 (2010).
Zhu, S. et al. Nlrp9b inflammasome restricts rotavirus infection in intestinal epithelial cells. Nature 546, 667–670 (2017).
Xu, H. et al. Innate immune sensing of bacterial modifications of Rho GTPases by the Pyrin inflammasome. Nature 513, 237–241 (2014).
Fernandes-Alnemri, T., Yu, J. W., Datta, P., Wu, J. & Alnemri, E. S. AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA. Nature 458, 509–513 (2009).
Hornung, V. et al. AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC. Nature 458, 514–518 (2009).
Kerur, N. et al. IFI16 acts as a nuclear pathogen sensor to induce the inflammasome in response to Kaposi Sarcoma-associated herpesvirus infection. Cell Host Microbe 9, 363–375 (2011).
Schroder, K. & Tschopp, J. The inflammasomes. Cell 140, 821–832 (2010).
Place, D. E. & Kanneganti, T. D. Recent advances in inflammasome biology. Curr. Opin. Immunol. 50, 32–38 (2018).
Duncan, J. A. et al. Cryopyrin/NALP3 binds ATP/dATP, is an ATPase, and requires ATP binding to mediate inflammatory signaling. Proc. Natl Acad. Sci. USA 104, 8041–8046 (2007).
Latz, E., Xiao, T. S. & Stutz, A. Activation and regulation of the inflammasomes. Nat. Rev. Immunol. 13, 397–411 (2013).
MacDonald, J. A., Wijekoon, C. P., Liao, K. C. & Muruve, D. A. Biochemical and structural aspects of the ATP-binding domain in inflammasome-forming human NLRP proteins. IUBMB Life 65, 851–862 (2013).
Juliana, C. et al. Anti-inflammatory compounds parthenolide and Bay 11–7082 are direct inhibitors of the inflammasome. J. Biol. Chem. 285, 9792–9802 (2010).
Marchetti, C. et al. OLT1177, a β-sulfonyl nitrile compound, safe in humans, inhibits the NLRP3 inflammasome and reverses the metabolic cost of inflammation. Proc. Natl Acad. Sci. USA 115, E1530–E1539 (2018).
Mastrocola, R. et al. Pharmacological inhibition of NLRP3 inflammasome attenuates myocardial ischemia/reperfusion injury by activation of RISK and mitochondrial pathways. Oxid. Med. Cell. Longev. 2016, 5271251 (2016).
Rathinam, V. A., Vanaja, S. K. & Fitzgerald, K. A. Regulation of inflammasome signaling. Nat. Immunol. 13, 333–342 (2012).
Mishra, B. B. et al. Nitric oxide controls the immunopathology of tuberculosis by inhibiting NLRP3 inflammasome-dependent processing of IL-1β. Nat. Immunol. 14, 52–60 (2013).
Stutz, A. et al. NLRP3 inflammasome assembly is regulated by phosphorylation of the pyrin domain. J. Exp. Med. 214, 1725–1736 (2017).
Allen, I. C. et al. The NLRP3 inflammasome mediates in vivo innate immunity to influenza A virus through recognition of viral RNA. Immunity 30, 556–565 (2009).
Kanneganti, T. D. et al. Critical role for Cryopyrin/Nalp3 in activation of caspase-1 in response to viral infection and double-stranded RNA. J. Biol. Chem. 281, 36560–36568 (2006).
Wu, J., Fernandes-Alnemri, T. & Alnemri, E. S. Involvement of the AIM2, NLRC4, and NLRP3 inflammasomes in caspase-1 activation by Listeria monocytogenes. J. Clin. Immunol. 30, 693–702 (2010).
Mariathasan, S. et al. Cryopyrin activates the inflammasome in response to toxins and ATP. Nature 440, 228–232 (2006).
Yamasaki, K. et al. NLRP3/cryopyrin is necessary for interleukin-1β (IL-1β) release in response to hyaluronan, an endogenous trigger of inflammation in response to injury. J. Biol. Chem. 284, 12762–12771 (2009).
Zhou, R., Tardivel, A., Thorens, B., Choi, I. & Tschopp, J. Thioredoxin-interacting protein links oxidative stress to inflammasome activation. Nat. Immunol. 11, 136–140 (2010).
Halle, A. et al. The NALP3 inflammasome is involved in the innate immune response to amyloid-beta. Nat. Immunol. 9, 857–865 (2008).
Dostert, C. et al. Innate immune activation through Nalp3 inflammasome sensing of asbestos and silica. Science 320, 674–677 (2008).
Hornung, V. et al. Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. Nat. Immunol. 9, 847–856 (2008).
Duewell, P. et al. NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals. Nature 464, 1357–1361 (2010).
Munoz-Planillo, R. et al. K+ efflux is the common trigger of NLRP3 inflammasome activation by bacterial toxins and particulate matter. Immunity 38, 1142–1153 (2013).
Gong, T., Yang, Y., Jin, T., Jiang, W. & Zhou, R. Orchestration of NLRP3 inflammasome activation by ion fluxes. Trends Immunol. 39, 393–406 (2018).
Petrilli, V. et al. Activation of the NALP3 inflammasome is triggered by low intracellular potassium concentration. Cell Death Differ. 14, 1583–1589 (2007).
Zhou, R., Yazdi, A. S., Menu, P. & Tschopp, J. A role for mitochondria in NLRP3 inflammasome activation. Nature 469, 221–225 (2011).
Zhong, Z. et al. New mitochondrial DNA synthesis enables NLRP3 inflammasome activation. Nature 560, 198–203 (2018).
He, Y., Zeng, M. Y., Yang, D., Motro, B. & Núñez, G. NEK7 is an essential mediator of NLRP3 activation downstream of potassium efflux. Nature 530, 354–357 (2016).
Shi, H. et al. NLRP3 activation and mitosis are mutually exclusive events coordinated by NEK7, a new inflammasome component. Nat. Immunol. 17, 250–258 (2016).
Gaidt, M. M. et al. The DNA inflammasome in human myeloid cells is initiated by a STING-cell death program upstream of NLRP3. Cell 171, 1110–1124 (2017).
Liston, A. & Masters, S. L. Homeostasis-altering molecular processes as mechanisms of inflammasome activation. Nat. Rev. Immunol. 17, 208–214 (2017).
Jourdan, T. et al. Activation of the Nlrp3 inflammasome in infiltrating macrophages by endocannabinoids mediates beta cell loss in type 2 diabetes. Nat. Med. 19, 1132–1140 (2013).
Inoue, M. et al. Interferon-β therapy against EAE is effective only when development of the disease depends on the NLRP3 inflammasome. Sci. Signal. 5, ra38 (2012).
Heneka, M. T. et al. NLRP3 is activated in Alzheimer’s disease and contributes to pathology in APP/PS1 mice. Nature 493, 674–678 (2013).
Vilaysane, A. et al. The NLRP3 inflammasome promotes renal inflammation and contributes to CKD. J. Am. Soc. Nephrol. 21, 1732–1744 (2010).
Chung, H. et al. NLRP3 regulates a non-canonical platform for caspase-8 activation during epithelial cell apoptosis. Cell Death Differ. 23, 1331–1346 (2016).
Lau, A. et al. Renal immune surveillance and dipeptidase-1 contribute to contrast-induced acute kidney injury. J. Clin. Invest. 128, 2894–2913 (2018).
Wang, W. et al. Inflammasome-independent NLRP3 augments TGF-beta signaling in kidney epithelium. J. Immunol. 190, 1239–1249 (2013).
Muruve, D. A. et al. The inflammasome recognizes cytosolic microbial and host DNA and triggers an innate immune response. Nature 452, 103–107 (2008).
Vilaysane, A. & Muruve, D. A. The innate immune response to DNA. Semin. Immunol. 21, 208–214 (2009).
Morrone, S. R. et al. Assembly-driven activation of the AIM2 foreign-dsDNA sensor provides a polymerization template for downstream ASC. Nat. Commun. 6, 7827 (2015).
Schneider, K. S. et al. The inflammasome drives GSDMD-independent secondary pyroptosis and IL-1 release in the absence of caspase-1 protease activity. Cell Rep. 21, 3846–3859 (2017).
Rathinam, V. A. et al. The AIM2 inflammasome is essential for host defense against cytosolic bacteria and DNA viruses. Nat. Immunol. 11, 395–402 (2010).
Saiga, H. et al. Critical role of AIM2 in Mycobacterium tuberculosis infection. Int. Immunol. 24, 637–644 (2012).
Yang, Y. et al. The AIM2 inflammasome is involved in macrophage activation during infection with virulent Mycobacterium bovis strain. J. Infect. Dis. 208, 1849–1858 (2013).
Belhocine, K. & Monack, D. M. Francisella infection triggers activation of the AIM2 inflammasome in murine dendritic cells. Cell. Microbiol. 14, 71–80 (2012).
Hu, B. et al. The DNA-sensing AIM2 inflammasome controls radiation-induced cell death and tissue injury. Science 354, 765–768 (2016).
Lian, Q. et al. Chemotherapy-induced intestinal inflammatory responses are mediated by exosome secretion of double-strand DNA via AIM2 inflammasome activation. Cell Res. 27, 784–800 (2017).
Di Micco, A. et al. AIM2 inflammasome is activated by pharmacological disruption of nuclear envelope integrity. Proc. Natl Acad. Sci. USA 113, E4671–E4680 (2016).
Heilig, R. & Broz, P. Function and mechanism of the pyrin inflammasome. Eur. J. Immunol. 48, 230–238 (2018).
Park, Y. H., Wood, G., Kastner, D. L. & Chae, J. J. Pyrin inflammasome activation and RhoA signaling in the autoinflammatory diseases FMF and HIDS. Nat. Immunol. 17, 914–921 (2016).
Anand, P. K. et al. NLRP6 negatively regulates innate immunity and host defence against bacterial pathogens. Nature 488, 389–393 (2012).
Cerretti, D. P. et al. Molecular cloning of the interleukin-1 beta converting enzyme. Science 256, 97–100 (1992).
Thornberry, N. A. et al. A novel heterodimeric cysteine protease is required for interleukin-1-beta processing in monocytes. Nature 356, 768–774 (1992).
Ghayur, T. et al. Caspase-1 processes IFN-gamma-inducing factor and regulates LPS-induced IFN-gamma production. Nature 386, 619–623 (1997).
Kayagaki, N. et al. Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling. Nature 526, 666–671 (2015).
Liu, X. et al. Inflammasome-activated gasdermin D causes pyroptosis by forming membrane pores. Nature 535, 153–158 (2016).
Netea, M. G. et al. Differential requirement for the activation of the inflammasome for processing and release of IL-1beta in monocytes and macrophages. Blood 113, 2324–2335 (2009).
Vigano, E. et al. Human caspase-4 and caspase-5 regulate the one-step non-canonical inflammasome activation in monocytes. Nat. Commun. 6, 8761 (2015).
Evavold, C. L. et al. The pore-forming protein gasdermin D regulates interleukin-1 secretion from living macrophages. Immunity 48, 35–44 (2018).
Ruhl, S. et al. ESCRT-dependent membrane repair negatively regulates pyroptosis downstream of GSDMD activation. Science 362, 956–960 (2018).
Rogers, C. et al. Cleavage of DFNA5 by caspase-3 during apoptosis mediates progression to secondary necrotic/pyroptotic cell death. Nat. Commun. 8, 14128 (2017).
Wang, Y. et al. Chemotherapy drugs induce pyroptosis through caspase-3 cleavage of a gasdermin. Nature 547, 99–103 (2017).
Man, S. M. et al. Salmonella infection induces recruitment of caspase-8 to the inflammasome to modulate IL-1β production. J. Immunol. 191, 5239–5246 (2013).
Vince, J. E. et al. Inhibitor of apoptosis proteins limit RIP3 kinase-dependent interleukin-1 activation. Immunity 36, 215–227 (2012).
Sagulenko, V. et al. AIM2 and NLRP3 inflammasomes activate both apoptotic and pyroptotic death pathways via ASC. Cell Death Differ. 20, 1149–1160 (2013).
Kayagaki, N. et al. Non-canonical inflammasome activation targets caspase-11. Nature 479, 117–121 (2011).
Schmid-Burgk, J. L. et al. Caspase-4 mediates non-canonical activation of the NLRP3 inflammasome in human myeloid cells. Eur. J. Immunol. 45, 2911–2917 (2015).
Shi, J. et al. Inflammatory caspases are innate immune receptors for intracellular LPS. Nature 514, 187–192 (2014).
Zanoni, I. et al. An endogenous caspase-11 ligand elicits interleukin-1 release from living dendritic cells. Science 352, 1232–1236 (2016).
Chu, L. H. et al. The oxidized phospholipid oxPAPC protects from septic shock by targeting the non-canonical inflammasome in macrophages. Nat. Commun. 9, 996 (2018).
Ruhl, S. & Broz, P. Caspase-11 activates a canonical NLRP3 inflammasome by promoting K+ efflux. Eur. J. Immunol. 45, 2927–2936 (2015).
Platnich, J. M. et al. Shiga toxin/lipopolysaccharide activates caspase-4 and gasdermin D to trigger mitochondrial reactive oxygen species upstream of the NLRP3 inflammasome. Cell Rep. 25, 1525–1536 (2018).
Pierini, R. et al. AIM2/ASC triggers caspase-8-dependent apoptosis in Francisella-infected caspase-1-deficient macrophages. Cell Death Differ. 19, 1709–1721 (2012).
Bakker, P. J. et al. A tissue-specific role for Nlrp3 in tubular epithelial repair after renal ischemia/reperfusion. Am. J. Pathol. 184, 2013–2022 (2014).
Bracey, N. A. et al. Mitochondrial NLRP3 protein induces reactive oxygen species to promote Smad protein signaling and fibrosis independent from the inflammasome. J. Biol. Chem. 289, 19571–19584 (2014).
Monteleone, M. et al. Interleukin-1beta maturation triggers its relocation to the plasma membrane for gasdermin-D-dependent and -independent secretion. Cell Rep. 24, 1425–1433 (2018).
Artlett, C. M. Inflammasomes in wound healing and fibrosis. J. Pathol. 229, 157–167 (2012).
Ben-Sasson, S. Z. et al. IL-1 enhances expansion, effector function, tissue localization, and memory response of antigen-specific CD8 T cells. J. Exp. Med. 210, 491–502 (2013).
Schneider, B. E. et al. A role for IL-18 in protective immunity against Mycobacterium tuberculosis. Eur. J. Immunol. 40, 396–405 (2010).
Harrison, O. J. et al. Epithelial-derived IL-18 regulates Th17 cell differentiation and Foxp3+ Treg cell function in the intestine. Mucosal Immunol. 8, 1226–1236 (2015).
Huber, S. et al. IL-22BP is regulated by the inflammasome and modulates tumorigenesis in the intestine. Nature 491, 259–263 (2012).
Chen, G. Y. Role of Nlrp6 and Nlrp12 in the maintenance of intestinal homeostasis. Eur. J. Immunol. 44, 321–327 (2014).
Longman, R. S. et al. CX3CR1+ mononuclear phagocytes support colitis-associated innate lymphoid cell production of IL-22. J. Exp. Med. 211, 1571–1583 (2014).
Martin, J. C. et al. Interleukin-22 binding protein (IL-22BP) is constitutively expressed by a subset of conventional dendritic cells and is strongly induced by retinoic acid. Mucosal Immunol. 7, 101–113 (2014).
Bruchard, M. et al. Corrigendum: the receptor NLRP3 is a transcriptional regulator of TH2 differentiation. Nat. Immunol. 16, 1292 (2015).
Bruchard, M. et al. The receptor NLRP3 is a transcriptional regulator of TH2 differentiation. Nat. Immunol. 16, 859–870 (2015).
Hu, S. et al. The DNA sensor AIM2 maintains intestinal homeostasis via regulation of epithelial antimicrobial host defense. Cell Rep. 13, 1922–1936 (2015).
Ratsimandresy, R. A., Indramohan, M., Dorfleutner, A. & Stehlik, C. The AIM2 inflammasome is a central regulator of intestinal homeostasis through the IL-18/IL-22/STAT3 pathway. Cell. Mol. Immunol. 14, 127–142 (2017).
Dupaul-Chicoine, J. et al. Control of intestinal homeostasis, colitis, and colitis-associated colorectal cancer by the inflammatory caspases. Immunity 32, 367–378 (2010).
Zaki, M. H. et al. The NLRP3 inflammasome protects against loss of epithelial integrity and mortality during experimental colitis. Immunity 32, 379–391 (2010).
Man, S. M. et al. Critical role for the DNA sensor AIM2 in stem cell proliferation and cancer. Cell 162, 45–58 (2015).
Wilson, J. E. et al. Inflammasome-independent role of AIM2 in suppressing colon tumorigenesis via DNA-PK and Akt. Nat. Med. 21, 906–913 (2015).
Krishnan, S. M. et al. Inflammasome activity is essential for one kidney/deoxycorticosterone acetate/salt-induced hypertension in mice. Br. J. Pharmacol. 173, 752–765 (2016).
Choubey, D. Absent in melanoma 2 proteins in the development of cancer. Cell. Mol. Life Sci. 73, 4383–4395 (2016).
Moon, J. S. et al. mTORC1-Induced HK1-dependent glycolysis regulates NLRP3 inflammasome activation. Cell Rep. 12, 102–115 (2015).
Wolf, A. J. et al. Hexokinase is an innate immune receptor for the detection of bacterial peptidoglycan. Cell 166, 624–636 (2016).
Xie, M. et al. PKM2-dependent glycolysis promotes NLRP3 and AIM2 inflammasome activation. Nat. Commun. 7, 13280 (2016).
Youm, Y. H. et al. The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease. Nat. Med. 21, 263–269 (2015).
Karasawa, T. et al. Saturated fatty acids undergo intracellular crystallization and activate the NLRP3 inflammasome in macrophages. Arterioscler. Thromb. Vasc. Biol. 38, 744–756 (2018).
Moon, J. S. et al. NOX4-dependent fatty acid oxidation promotes NLRP3 inflammasome activation in macrophages. Nat. Med. 22, 1002–1012 (2016).
Vandanmagsar, B. et al. The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance. Nat. Med. 17, 179–188 (2011).
Edelstein, C. L. et al. Proximal tubules from caspase-1-deficient mice are protected against hypoxia-induced membrane injury. Nephrol. Dial. Transplant. 22, 1052–1061 (2007).
Melnikov, V. Y. et al. Neutrophil-independent mechanisms of caspase-1- and IL-18-mediated ischemic acute tubular necrosis in mice. J. Clin. Invest. 110, 1083–1091 (2002).
Bani-Hani, A. H. et al. IL-18 neutralization ameliorates obstruction-induced epithelial-mesenchymal transition and renal fibrosis. Kidney Int. 76, 500–511 (2009).
Yamanishi, K. et al. Interleukin-18-deficient mice develop dyslipidemia resulting in nonalcoholic fatty liver disease and steatohepatitis. Transl Res. 173, 101–114 (2016).
Yamanishi, K. et al. Physiological and molecular effects of interleukin-18 administration on the mouse kidney. J. Transl Med. 16, 51 (2018).
Lichtnekert, J. et al. Anti-GBM glomerulonephritis involves IL-1 but is independent of NLRP3/ASC inflammasome-mediated activation of caspase-1. PLOS ONE 6, e26778 (2011).
Chun, J. et al. NLRP3 localizes to the tubular epithelium in human kidney and correlates with outcome in IgA nephropathy. Sci. Rep. 6, 24667 (2016).
Anders, H. J. et al. The macrophage phenotype and inflammasome component NLRP3 contributes to nephrocalcinosis-related chronic kidney disease independent from IL-1-mediated tissue injury. Kidney Int. 93, 656–669 (2018).
DeWolf, S. E. et al. Expression of TLR2, NOD1, and NOD2 and the NLRP3 inflammasome in renal tubular epithelial cells of male versus female mice. Nephron 137, 68–76 (2017).
Romero, C. A. et al. Uric acid activates NRLP3 inflammasome in an in-vivo model of epithelial to mesenchymal transition in the kidney. J. Mol. Histol. 48, 209–218 (2017).
Man, S. M. et al. Inflammasome activation causes dual recruitment of NLRC4 and NLRP3 to the same macromolecular complex. Proc. Natl Acad. Sci. USA 111, 7403–7408 (2014).
Anders, H. J. & Muruve, D. A. The inflammasomes in kidney disease. J. Am. Soc. Nephrol. 22, 1007–1018 (2011).
Komada, T. et al. ASC in renal collecting duct epithelial cells contributes to inflammation and injury after unilateral ureteral obstruction. Am. J. Pathol. 184, 1287–1298 (2014).
Pulskens, W. P. et al. Nlrp3 prevents early renal interstitial edema and vascular permeability in unilateral ureteral obstruction. PLOS ONE 9, e85775 (2014).
Correa-Costa, M. et al. Pivotal role of Toll-like receptors 2 and 4, its adaptor molecule MyD88, and inflammasome complex in experimental tubule-interstitial nephritis. PLOS ONE 6, e29004 (2011).
Bakker, P. J. et al. Nlrp3 is a key modulator of diet-induced nephropathy and renal cholesterol accumulation. Kidney Int. 85, 1112–1122 (2014).
Solini, A. et al. The purinergic 2X7 receptor participates in renal inflammation and injury induced by high-fat diet: possible role of NLRP3 inflammasome activation. J. Pathol. 231, 342–353 (2013).
Zhang, C. et al. Activation of Nod-like receptor protein 3 inflammasomes turns on podocyte injury and glomerular sclerosis in hyperhomocysteinemia. Hypertension 60, 154–162 (2012).
Zhuang, Y. et al. NLRP3 inflammasome mediates albumin-induced renal tubular injury through impaired mitochondrial function. J. Biol. Chem. 289, 25101–25111 (2014).
Wen, Y. et al. NLRP3 inflammasome activation is involved in Ang II-induced kidney damage via mitochondrial dysfunction. Oncotarget 7, 54290–54302 (2016).
Cao, Y. et al. Role of the nucleotide-binding domain-like receptor protein 3 inflammasome in acute kidney injury. FEBS J. 282, 3799–3807 (2015).
Shahzad, K. et al. Nlrp3-inflammasome activation in non-myeloid-derived cells aggravates diabetic nephropathy. Kidney Int. 87, 74–84 (2015).
Andersen, K., Eltrich, N., Lichtnekert, J., Anders, H. J. & Vielhauer, V. The NLRP3/ASC inflammasome promotes T cell-dependent immune complex glomerulonephritis by canonical and noncanonical mechanisms. Kidney Int. 86, 965–978 (2014).
Gong, W. et al. NLRP3 deletion protects against renal fibrosis and attenuates mitochondrial abnormality in mouse with 5/6 nephrectomy. Am. J. Physiol. Renal Physiol. 310, F1081–F1088 (2016).
Yu, G. et al. The NLRP3 inflammasome is a potential target of ozone therapy aiming to ease chronic renal inflammation in chronic kidney disease. Int. Immunopharmacol. 43, 203–209 (2017).
Iyer, S. S. et al. Necrotic cells trigger a sterile inflammatory response through the Nlrp3 inflammasome. Proc. Natl Acad. Sci. USA 106, 20388–20393 (2009).
Nazir, S. et al. Cytoprotective activated protein C averts Nlrp3 inflammasome-induced ischemia-reperfusion injury via mTORC1 inhibition. Blood 130, 2664–2677 (2017).
Shigeoka, A. A. et al. An inflammasome-independent role for epithelial-expressed Nlrp3 in renal ischemia-reperfusion injury. J. Immunol. 185, 6277–6285 (2010).
Tang, T. T. et al. Hydroxychloroquine attenuates renal ischemia/reperfusion injury by inhibiting cathepsin mediated NLRP3 inflammasome activation. Cell Death Dis. 9, 351 (2018).
Subramanian, N., Natarajan, K., Clatworthy, M. R., Wang, Z. & Germain, R. N. The adaptor MAVS promotes NLRP3 mitochondrial localization and inflammasome activation. Cell 153, 348–361 (2013).
Kim, H. J. et al. NLRP3 inflammasome knockout mice are protected against ischemic but not cisplatin-induced acute kidney injury. J. Pharmacol. Exp. Ther. 346, 465–472 (2013).
Komada, T. et al. Role of NLRP3 inflammasomes for rhabdomyolysis-induced acute kidney injury. Sci. Rep. 5, 10901 (2015).
Shen, J. et al. NLRP3 inflammasome mediates contrast media-induced acute kidney injury by regulating cell apoptosis. Sci. Rep. 6, 34682 (2016).
Zhang, Z. et al. Caspase-11-mediated tubular epithelial pyroptosis underlies contrast-induced acute kidney injury. Cell Death Dis. 9, 983 (2018).
Linkermann, A. et al. The RIP1-kinase inhibitor necrostatin-1 prevents osmotic nephrosis and contrast-induced AKI in mice. J. Am. Soc. Nephrol. 24, 1545–1557 (2013).
Wang, W. et al. Endotoxemic acute renal failure is attenuated in caspase-1-deficient mice. Am. J. Physiol. Renal Physiol. 288, F997–F1004 (2005).
Purves, J. T. & Hughes, F. M. Jr. Inflammasomes in the urinary tract: a disease-based review. Am. J. Physiol. Renal Physiol. 311, F653–F662 (2016).
Wang, M. J., Liu, Q. L. & Liu, C. H. Correlation of CCR5 and NLRP3 gene polymorphisms with renal damage due to hepatitis C virus-related cryoglobulinemia. Exp. Ther. Med. 16, 3055–3059 (2018).
Feria, M. G., Taborda, N. A., Hernandez, J. C. & Rugeles, M. T. HIV replication is associated to inflammasomes activation, IL-1 beta, IL-18 and caspase-1 expression in GALT and peripheral blood. PLOS ONE 13, e0192845 (2018).
Hernandez, J. C., Latz, E. & Urcuqui-Inchima, S. HIV-1 induces the first signal to activate the NLRP3 inflammasome in monocyte-derived macrophages. Intervirology 57, 36–42 (2014).
Doitsh, G. et al. Cell death by pyroptosis drives CD4 T cell depletion in HIV-1 infection. Nature 505, 509–514 (2014).
Galloway, N. L. K. et al. Cell-to-cell transmission of HIV-1 is required to trigger pyroptotic death of lymphoid-tissue-derived CD4 T cells. Cell Rep. 12, 1555–1563 (2015).
Monroe, K. M. et al. IFI16 DNA sensor is required for death of lymphoid CD4 T cells abortively infected with HIV. Science 343, 428–432 (2014).
Haque, S. et al. HIV promotes NLRP3 inflammasome complex activation in murine HIV-associated nephropathy. Am. J. Pathol. 186, 347–358 (2016).
Mulay, S. R. & Anders, H. J. Crystal nephropathies: mechanisms of crystal-induced kidney injury. Nat. Rev. Nephrol. 13, 226–240 (2017).
Mulay, S. R. et al. Calcium oxalate crystals induce renal inflammation by NLRP3-mediated IL-1β secretion. J. Clin. Invest. 123, 236–246 (2013).
Prencipe, G. et al. Inflammasome activation by cystine crystals: implications for the pathogenesis of cystinosis. J. Am. Soc. Nephrol. 25, 1163–1169 (2014).
Darisipudi, M. N. et al. Uromodulin triggers IL-1β-dependent innate immunity via the NLRP3 inflammasome. J. Am. Soc. Nephrol. 23, 1783–1789 (2012).
Timoshanko, J. R., Kitching, A. R., Iwakura, Y., Holdsworth, S. R. & Tipping, P. G. Contributions of IL-1β and IL-1α to crescentic glomerulonephritis in mice. J. Am. Soc. Nephrol. 15, 910–918 (2004).
Shahzad, K. et al. Caspase-1, but not caspase-3, promotes diabetic nephropathy. J. Am. Soc. Nephrol. 27, 2270–2275 (2016).
Xia, M., Conley, S. M., Li, G., Li, P. L. & Boini, K. M. Inhibition of hyperhomocysteinemia-induced inflammasome activation and glomerular sclerosis by NLRP3 gene deletion. Cell Physiol. Biochem. 34, 829–841 (2014).
Abais, J. M. et al. Nod-like receptor protein 3 (NLRP3) inflammasome activation and podocyte injury via thioredoxin-interacting protein (TXNIP) during hyperhomocysteinemia. J. Biol. Chem. 289, 27159–27168 (2014).
Beckerman, P. et al. Transgenic expression of human APOL1 risk variants in podocytes induces kidney disease in mice. Nat. Med. 23, 429–438 (2017).
Yu, J. W. et al. Pyrin activates the ASC pyroptosome in response to engagement by autoinflammatory PSTPIP1 mutants. Mol. Cell 28, 214–227 (2007).
Wang, S. et al. Interleukin-22 ameliorated renal injury and fibrosis in diabetic nephropathy through inhibition of NLRP3 inflammasome activation. Cell Death Dis. 8, e2937 (2017).
Mahajan, V. S. et al. Striking immune phenotypes in gene-targeted mice are driven by a copy-number variant originating from a commercially available C57BL/6 strain. Cell Rep. 15, 1901–1909 (2016).
Ulland, T. K. et al. Nlrp12 mutation causes C57BL/6J strain-specific defect in neutrophil recruitment. Nat. Commun. 7, 13180 (2016).
Yang, H. et al. Subspecific origin and haplotype diversity in the laboratory mouse. Nat. Genet. 43, 648–655 (2011).
Lu, L. H. et al. Increased macrophage infiltration and fractalkine expression in cisplatin-induced acute renal failure in mice. J. Pharmacol. Exp. Ther. 324, 111–117 (2008).
Tadagavadi, R. K. & Reeves, W. B. Renal dendritic cells ameliorate nephrotoxic acute kidney injury. J. Am. Soc. Nephrol. 21, 53–63 (2010).
Denes, A. et al. AIM2 and NLRC4 inflammasomes contribute with ASC to acute brain injury independently of NLRP3. Proc. Natl Acad. Sci. USA 112, 4050–4055 (2015).
Guo, Q. et al. Cytokine secretion and pyroptosis of thyroid follicular cells mediated by enhanced NLRP3, NLRP1, NLRC4, and AIM2 inflammasomes are associated with autoimmune thyroiditis. Front. Immunol. 9, 1197 (2018).
Zhen, J. et al. AIM2 mediates inflammation-associated renal damage in hepatitis B virus-associated glomerulonephritis by regulating caspase-1, IL-1β, and IL-18. Mediators Inflamm. 2014, 190860 (2014).
Zhang, W. et al. AIM2 facilitates the apoptotic DNA-induced systemic lupus erythematosus via arbitrating macrophage functional maturation. J. Clin. Immunol. 33, 925–937 (2013).
Komada, T. et al. Macrophage uptake of necrotic cell DNA activates the AIM2 inflammasome to regulate a proinflammatory phenotype in CKD. J. Am. Soc. Nephrol. 29, 1165–1181 (2018).
Yuan, F. et al. Involvement of the NLRC4-inflammasome in diabetic nephropathy. PLOS ONE 11, e0164135 (2016).
Meissner, T. B. et al. NLR family member NLRC5 is a transcriptional regulator of MHC class I genes. Proc. Natl Acad. Sci. USA 107, 13794–13799 (2010).
Li, Q. et al. NLRC5 deficiency protects against acute kidney injury in mice by mediating carcinoembryonic antigen-related cell adhesion molecule 1 signaling. Kidney Int. 94, 551–566 (2018).
Nagaishi, T. et al. SHP1 phosphatase-dependent T cell inhibition by CEACAM1 adhesion molecule isoforms. Immunity 25, 769–781 (2006).
Luan, P. et al. NLRC5 deficiency ameliorates diabetic nephropathy through alleviating inflammation. FASEB J. 32, 1070–1084 (2018).
Moore, C. B. et al. NLRX1 is a regulator of mitochondrial antiviral immunity. Nature 451, 573–577 (2008).
Arnoult, D. et al. An N-terminal addressing sequence targets NLRX1 to the mitochondrial matrix. J. Cell Sci. 122, 3161–3168 (2009).
Stokman, G. et al. NLRX1 dampens oxidative stress and apoptosis in tissue injury via control of mitochondrial activity. J. Exp. Med. 214, 2405–2420 (2017).
Strowig, T., Henao-Mejia, J., Elinav, E. & Flavell, R. Inflammasomes in health and disease. Nature 481, 278–286 (2012).
Magitta, N. F. et al. A coding polymorphism in NALP1 confers risk for autoimmune Addison’s disease and type 1 diabetes. Genes Immun. 10, 120–124 (2009).
Pontillo, A. et al. Polimorphisms in inflammasome genes are involved in the predisposition to systemic lupus erythematosus. Autoimmunity 45, 271–278 (2012).
Pontillo, A., Reis, E. C., Liphaus, B. L., Silva, C. A. & Carneiro-Sampaio, M. Inflammasome polymorphisms in juvenile systemic lupus erythematosus. Autoimmunity 48, 434–437 (2015).
Pontillo, A. et al. Two SNPs in NLRP3 gene are involved in the predisposition to type-1 diabetes and celiac disease in a pediatric population from northeast Brazil. Autoimmunity 43, 583–589 (2010).
Ito, S., Hara, Y. & Kubota, T. CARD8 is a negative regulator for NLRP3 inflammasome, but mutant NLRP3 in cryopyrin-associated periodic syndromes escapes the restriction. Arthritis Res. Ther. 16, R52 (2014).
Liu, R. et al. Novel genes and variants associated with IgA nephropathy by co-segregating with the disease phenotypes in 10 IgAN families. Gene 571, 43–51 (2015).
Granata, S. et al. NLRP3 inflammasome activation in dialyzed chronic kidney disease patients. PLOS ONE 10, e0122272 (2015).
Muruve, D. A. et al. The biobank for the molecular classification of kidney disease: research translation and precision medicine in nephrology. BMC Nephrol. 18, 252 (2017).
Ulke-Lemee, A. et al. Quantification of inflammasome adaptor protein ASC in biological samples by multiple-reaction monitoring mass spectrometry. Inflammation 41, 1396–1408 (2018).
Fu, R. et al. Podocyte activation of NLRP3 inflammasomes contributes to the development of proteinuria in lupus nephritis. Arthritis Rheumatol. 69, 1636–1646 (2017).
Balasubramaniam, G., Almond, M. & Dasgupta, B. Improved renal function in diabetic patients with acute gout treated with anakinra. Kidney Int. 88, 195–196 (2015).
Larsen, C. M. et al. Interleukin-1-receptor antagonist in type 2 diabetes mellitus. N. Engl. J. Med. 356, 1517–1526 (2007).
Milhavet, F. et al. The infevers autoinflammatory mutation online registry: update with new genes and functions. Hum. Mutat. 29, 803–808 (2008).
Cordero, M. D., Alcocer-Gomez, E. & Ryffel, B. Gain of function mutation and inflammasome driven diseases in human and mouse models. J. Autoimmun. 91, 13–22 (2018).
French, F. M. F. C. A candidate gene for familial Mediterranean fever. Nat. Genet. 17, 25–31 (1997).
Chang, C. The pathogenesis of neonatal autoimmune and autoinflammatory diseases: a comprehensive review. J. Autoimmun. 41, 100–110 (2013).
Scarpioni, R. et al. Renal involvement in secondary amyloidosis of Muckle-Wells syndrome: marked improvement of renal function and reduction of proteinuria after therapy with human anti-interleukin-1β monoclonal antibody canakinumab. Clin. Rheumatol. 34, 1311–1316 (2015).
Neven, B. et al. Long-term efficacy of the interleukin-1 receptor antagonist anakinra in ten patients with neonatal-onset multisystem inflammatory disease/chronic infantile neurologic, cutaneous, articular syndrome. Arthritis Rheum. 62, 258–267 (2010).
Omi, T. et al. An intronic variable number of tandem repeat polymorphisms of the cold-induced autoinflammatory syndrome 1 (CIAS1) gene modifies gene expression and is associated with essential hypertension. Eur. J. Hum. Genet. 14, 1295–1305 (2006).
Johansson, A. et al. NLRC4 inflammasome is an important regulator of interleukin-18 levels in patients with acute coronary syndromes: genome-wide association study in the PLATelet inhibition and patient Outcomes Trial (PLATO). Circ. Cardiovasc. Genet. 8, 498–506 (2015).
Furman, D. et al. Expression of specific inflammasome gene modules stratifies older individuals into two extreme clinical and immunological states. Nat. Med. 23, 174–184 (2017).
Bachove, I. & Chang, C. Anakinra and related drugs targeting interleukin-1 in the treatment of cryopyrin- associated periodic syndromes. Open Access Rheumatol. 6, 15–25 (2014).
Ottaviani, S. et al. Efficacy of anakinra in gouty arthritis: a retrospective study of 40 cases. Arthritis Res. Ther. 15, R123 (2013).
Loustau, C. et al. Effectiveness and safety of anakinra in gout patients with stage 4–5 chronic kidney disease or kidney transplantation: a multicentre, retrospective study. Joint Bone Spine 85, 755–760 (2018).
Hoffman, H. M. et al. Efficacy and safety of rilonacept (interleukin-1 Trap) in patients with cryopyrin-associated periodic syndromes: results from two sequential placebo-controlled studies. Arthritis Rheum. 58, 2443–2452 (2008).
Sundy, J. S. et al. Rilonacept for gout flare prevention in patients receiving uric acid-lowering therapy: results of RESURGE, a phase III, international safety study. J. Rheumatol. 41, 1703–1711 (2014).
Lachmann, H. J. et al. Use of canakinumab in the cryopyrin-associated periodic syndrome. N. Engl. J. Med. 360, 2416–2425 (2009).
Ridker, P. M. et al. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N. Engl. J. Med. 377, 1119–1131 (2017).
Ridker, P. M. et al. Inhibition of interleukin-1β by canakinumab and cardiovascular outcomes in patients with chronic kidney disease. J. Am. Coll. Cardiol. 71, 2405–2414 (2018).
Homsi, E., Janino, P. & de Faria, J. B. Role of caspases on cell death, inflammation, and cell cycle in glycerol-induced acute renal failure. Kidney Int. 69, 1385–1392 (2006).
Sogawa, Y. et al. Infiltration of M1, but not M2, macrophages is impaired after unilateral ureter obstruction in Nrf2-deficient mice. Sci. Rep. 7, 8801 (2017).
Bialer, M. et al. Progress report on new antiepileptic drugs: a summary of the Eleventh Eilat Conference (EILAT XI). Epilepsy Res. 103, 2–30 (2013).
Zaki, M. H., Vogel, P., Body-Malapel, M., Lamkanfi, M. & Kanneganti, T. D. IL-18 production downstream of the Nlrp3 inflammasome confers protection against colorectal tumor formation. J. Immunol. 185, 4912–4920 (2010).
Yang, J. et al. Mechanism of gasdermin D recognition by inflammatory caspases and their inhibition by a gasdermin D-derived peptide inhibitor. Proc. Natl Acad. Sci. USA 115, 6792–6797 (2018).
Hu, J. J. et al. Identification of pyroptosis inhibitors that target a reactive cysteine in gasdermin D. Preprint at bioRxiv https://doi.org/10.1101/365908 (2018).
Lamkanfi, M. et al. Glyburide inhibits the cryopyrin/Nalp3 inflammasome. J. Cell Biol. 187, 61–70 (2009).
Perregaux, D. G. et al. Identification and characterization of a novel class of interleukin-1 post-translational processing inhibitors. J. Pharmacol. Exp. Ther. 299, 187–197 (2001).
Coll, R. C. et al. A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases. Nat. Med. 21, 248–255 (2015).
Primiano, M. J. et al. Efficacy and pharmacology of the NLRP3 inflammasome inhibitor CP-456,773 (CRID3) in murine models of dermal and pulmonary inflammation. J. Immunol. 197, 2421–2433 (2016).
Ludwig-Portugall, I. et al. An NLRP3-specific inflammasome inhibitor attenuates crystal-induced kidney fibrosis in mice. Kidney Int. 90, 525–539 (2016).
Ummarino, D. Lupus nephritis: NLRP3 inflammasome ignites podocyte dysfunction. Nat. Rev. Rheumatol. 13, 451 (2017).
Strickson, S. et al. The anti-inflammatory drug BAY 11–7082 suppresses the MyD88-dependent signalling network by targeting the ubiquitin system. Biochem. J. 451, 427–437 (2013).
Zhao, J. et al. Bay11-7082 attenuates murine lupus nephritis via inhibiting NLRP3 inflammasome and NF-κB activation. Int. Immunopharmacol. 17, 116–122 (2013).
Kolati, S. R. et al. BAY 11–7082 ameliorates diabetic nephropathy by attenuating hyperglycemia-mediated oxidative stress and renal inflammation via NF-κB pathway. Environ. Toxicol. Pharmacol. 39, 690–699 (2015).
Marchetti, C. et al. A novel pharmacologic inhibitor of the NLRP3 inflammasome limits myocardial injury after ischemia-reperfusion in the mouse. J. Cardiovasc. Pharmacol. 63, 316–322 (2014).
Huang, Y. et al. Tranilast directly targets NLRP3 to treat inflammasome-driven diseases. EMBO Mol. Med. 10, e8689 (2018).
Jiang, H. et al. Identification of a selective and direct NLRP3 inhibitor to treat inflammatory disorders. J. Exp. Med. 214, 3219–3238 (2017).
Leung, Y. Y., Yao Hui, L. L. & Kraus, V. B. Colchicine—update on mechanisms of action and therapeutic uses. Semin. Arthritis Rheum. 45, 341–350 (2015).
Zheng, L. et al. Fluorofenidone attenuates interleukin-1beta production by interacting with NLRP3 inflammasome in unilateral ureteral obstruction. Nephrology (Carlton) 23, 573–584 (2018).
Lee, H. E. et al. Targeting ASC in NLRP3 inflammasome by caffeic acid phenethyl ester: a novel strategy to treat acute gout. Sci. Rep. 6, 38622 (2016).
Martinez, G. J., Celermajer, D. S. & Patel, S. The NLRP3 inflammasome and the emerging role of colchicine to inhibit atherosclerosis-associated inflammation. Atherosclerosis 269, 262–271 (2018).
Ozen, S. et al. EULAR recommendations for the management of familial Mediterranean fever. Ann. Rheum. Dis. 75, 644–651 (2016).
Ito, H., Kanbe, A., Sakai, H. & Seishima, M. Activation of NLRP3 signalling accelerates skin wound healing. Exp. Dermatol. 27, 80–86 (2018).
Juliana, C. et al. Non-transcriptional priming and deubiquitination regulate NLRP3 inflammasome activation. J. Biol. Chem. 287, 36617–36622 (2012).
Boucher, D. et al. Caspase-1 self-cleavage is an intrinsic mechanism to terminate inflammasome activity. J. Exp. Med. 215, 827–840 (2018).
Swanson, K. V. et al. A noncanonical function of cGAMP in inflammasome priming and activation. J. Exp. Med. 214, 3611–3626 (2017).
Eugenia Schroeder, M. et al. Pro-inflammatory Ca2+-activated K+ channels are inhibited by hydroxychloroquine. Sci. Rep. 7, 1892 (2017).
Lech, M., Avila-Ferrufino, A., Skuginna, V., Susanti, H. E. & Anders, H. J. Quantitative expression of RIG-like helicase, NOD-like receptor and inflammasome-related mRNAs in humans and mice. Int. Immunol. 22, 717–728 (2010).
Kadoya, H. et al. Excess aldosterone is a critical danger signal for inflammasome activation in the development of renal fibrosis in mice. FASEB J. 29, 3899–3910 (2015).
Masumoto, J. et al. Expression of apoptosis-associated speck-like protein containing a caspase recruitment domain, a pyrin N-terminal homology domain-containing protein, in normal human tissues. J. Histochem. Cytochem. 49, 1269–1275 (2001).
Gauer, S. et al. IL-18 is expressed in the intercalated cell of human kidney. Kidney Int. 72, 1081–1087 (2007).
Chan, A. J. et al. Innate IL-17A-producing leukocytes promote acute kidney injury via inflammasome and Toll-like receptor activation. Am. J. Pathol. 184, 1411–1418 (2014).
Faubel, S. et al. Caspase-1-deficient mice are protected against cisplatin-induced apoptosis and acute tubular necrosis. Kidney Int. 66, 2202–2213 (2004).
Kiryluk, K. et al. Discovery of new risk loci for IgA nephropathy implicates genes involved in immunity against intestinal pathogens. Nat. Genet. 46, 1187–1196 (2014).
Sayanthooran, S., Magana-Arachchi, D. N., Gunerathne, L., Abeysekera, T. D. & Sooriyapathirana, S. S. Upregulation of oxidative stress related genes in a chronic kidney disease attributed to specific geographical locations of Sri Lanka. Biomed. Res. Int. 2016, 7546265 (2016).
Dessing, M. C. et al. Donor and recipient genetic variants in NLRP3 associate with early acute rejection following kidney transplantation. Sci. Rep. 6, 36315 (2016).
The authors’ work was supported by operating grants from the Canadian Institutes for Health Research (CIHR) and the Kidney Foundation of Canada and by a team grant under the CIHR Inflammation in Chronic Disease Signature Initiative. D.A.M. holds a Tier II Canada Research Chair. T.K. was supported by a fellowship from the Manpei Suzuki Diabetes Foundation, Japan. The authors thank J. Chun (University of Calgary) for critical review of the manuscript before submission.
Nature Reviews Nephrology thanks B. Isermann, D. Mattson, A. Zhang and the other anonymous reviewer(s) for their contribution to the peer review of this work.
The authors declare no competing interests.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
- Pathogen-associated molecular patterns
(PAMPs). Molecular structures produced by pathogens and recognized as foreign to trigger innate immune responses.
- Danger-associated molecular patterns
(DAMPs). Endogenous molecules released by damaged or necrotic cells and recognized as a ‘danger’ signal to trigger innate immune responses.
A type of regulated cell death that depends on the formation of plasma membrane pores by gasdermin D. This process often occurs as a consequence of activation of inflammatory caspases such as caspase 1, caspase 4, caspase 5 and caspase 11.
- Post-apoptotic secondary necrosis
The process of cell membrane degradation with the release of cell components following apoptotic cell death.
- Secondary pyroptosis
A gasdermin-D-independent lytic form of cell death with a feature of pyroptosis such as IL-1β-release.
- TH2 cells
T helper 2 (TH2) cells are a subset of CD4+ effector T lymphocytes that produce cytokines such as IL-4, IL-5, IL-6, IL-9, IL-13 and IL-25. TH2 cells are critical for immune responses against parasites and trigger allergic inflammation in diseases such as asthma.
- Ketone body
An endogenous product of fatty acid oxidation, which occurs in the liver when carbohydrates are scarce. The three ketone bodies are acetoacetates, β-hydroxybutyrate and acetone.
- Type II apoptotic cells
In type II apoptotic cells, caspase 8 activation at the death-inducing signalling complex is inhibited by the caspase 3 inhibitor X-linked inhibitor of apoptosis and cellular FLICE inhibitory protein (cFLIP). Type II cells require the mitochondrial pathway to fully initiate the cell death programme via caspase 8 activation at the outer mitochondrial membrane.
- Type I apoptotic cells
Type I apoptotic cells activate caspase 8 directly via recruitment to the death-inducing signalling complex at the plasma membrane. This complex acts directly on the executioner caspase 3 to initiate apoptosis.
- High-sensitivity C-reactive protein
(hsCRP). An acute phase protein that is released from the liver during bacterial infection, tissue inflammation and trauma.
- Honeybee propolis
A natural resinous mixture produced by honeybees from materials collected from plants.
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Komada, T., Muruve, D.A. The role of inflammasomes in kidney disease. Nat Rev Nephrol 15, 501–520 (2019). https://doi.org/10.1038/s41581-019-0158-z
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