Pyroptosis as Inflammatory Cell Death

Pyroptosis, caspase-1-dependent inflammatory cell death, is induced by intracellular pathogens or tissue lesions. Procaspase-1 activation, which is essential for the processing of proinflammatory cytokines pro-IL-1β and pro-IL-18, occurs in macromolecular protein complexes, also referred to as inflammasomes. In the gram-negative bacilli-induced infections inflammasome assembly incorporates caspase-4 and caspase-5. Originally identified as a protective mechanism of innate immunity, at present pyroptosis is not limited to the inhibition of intracellular pathogen multiplication. The current review discusses molecular mechanisms of pyroptosis-like cell death and possible pyroptosis involvement in tumor cell death.

• Amaliya Artashevna Vartanyan NN Blokhin National Medical Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478 ; ФГБУ «НМИЦ онкологии им. Н.Н. Блохина» Минздрава России, Каширское ш., д. 24, Москва, Российская Федерация, 115478
• V.S. Kosorukov NN Blokhin National Medical Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478 ; ФГБУ «НМИЦ онкологии им. Н.Н. Блохина» Минздрава России, Каширское ш., д. 24, Москва, Российская Федерация, 115478

1. Zychlinsky A, Prevost MC, Sansonetti PJ. Shigella flexneri induces apoptosis in infected macrophages. Nature. 1992;358(6382):167–9. doi: 10.1038/358167a0. DOI: https://doi.org/10.1038/358167a0
2. Brennan MA, Cookson BT. Salmonella induces macrophage death by caspase-1-dependent necrosis. Mol Microbiol. 2000;38(1):31–40. doi: 10.1046/j.1365-2958.2000.02103.x. DOI: https://doi.org/10.1046/j.1365-2958.2000.02103.x
3. Cookson BT, Brennan MA. Pro-inflammatory programmed cell death. Trends Microbiol. 2001;9(3):113–4. doi: 10.1016/s0966-842x(00)01936-3. DOI: https://doi.org/10.1016/S0966-842X(00)01936-3
4. Li P, Allen H, Banerjee S, et al. Mice deficient in IL-1 beta-converting enzyme are defective in production of mature IL-1 beta and resistant to endotoxic shock. Cell. 1995;80(3):401–11. doi: 10.1016/0092-8674(95)90490-5. DOI: https://doi.org/10.1016/0092-8674(95)90490-5
5. Yuan YY, Xie KX, Wang SL, et al. Inflammatory caspase-related pyroptosis: mechanism, regulation and therapeutic potential for inflammatory bowel disease. Gastroenterology Report. 2018;6(3):167–76. doi: 10.1093/gastro/goy011. DOI: https://doi.org/10.1093/gastro/goy011
6. Doitsh G, Cavrois M, Lassen KG, et al. Abortive HIV infection mediates CD4 T cell depletion and inflammation in human lymphoid tissue. Cell. 2010;143(5):789–801. doi: 10.1016/j.cell.2010.11.001. DOI: https://doi.org/10.1016/j.cell.2010.11.001
7. Franchi L, Warner N, Viani K, et al. Function of Nod-like receptors in microbial recognition and host defense. Immunol Rev. 2009;227(1):106–28. doi: 10.1111/j.1600-065x.2008.00734.x. DOI: https://doi.org/10.1111/j.1600-065X.2008.00734.x
8. Bortoluci KR, Medzhitov R. Control of infection by pyroptosis and autophagy: role of TLR and NLR. Cell Mol Life Sci. 2010;67(10):1643–51. doi: 10.1007/s00018-010-0335-5. DOI: https://doi.org/10.1007/s00018-010-0335-5
9. Lamkanfi M, Dixit V. Mechanisms and functions of inflammasomes. Cell. 2014;157(5):1013–22. doi: 10.1016/j.cell.2014.04.007. DOI: https://doi.org/10.1016/j.cell.2014.04.007
10. Man SM, Karki R, Kanneganti TD. Molecular mechanisms and functions of pyroptosis, inflammatory caspases and inflammasomes in infectious diseases. Immunol Rev. 2017;277(1):61–75. doi: 10.1111/imr.12534. DOI: https://doi.org/10.1111/imr.12534
11. Malireddi RK, Ippagunta S, Lamkanfi M, et al. Cutting edge: proteolytic inactivation of poly(ADP-ribose) polymerase 1 by the Nlrp3 and Nlrc4 inflammasomes. J Immunol. 2010;185(6):3127–30. doi: 10.4049/jimmunol.1001512. DOI: https://doi.org/10.4049/jimmunol.1001512
12. Kovacs SB, Miao EA. Gasdermins: Effectors of Pyroptosis. Trends Cell Biol. 2017;27(9):673–84. doi: 10.1016/j.tcb.2017.05.005. DOI: https://doi.org/10.1016/j.tcb.2017.05.005
13. Feng S, Fox D, Man SM. Mechanisms of Gasdermin Family Members in Inflammasome Signaling and Cell Death. J Mol Biol. 2018;430(18):3068–80. doi: 10.1016/j.jmb.2018.07.002. DOI: https://doi.org/10.1016/j.jmb.2018.07.002
14. Prajwal G, Lukens JR, Thirumala-Devi K. Mitochondria: diversity in the regulation of the NLRP3 inflammasome. Trends Mol Med. 2015;21(3):193–201. doi: 10.1016/j.molmed.2014.11.008. DOI: https://doi.org/10.1016/j.molmed.2014.11.008
15. Yu J, Nagasu H, Murakami T, et al. Inflammasome activation leads to Caspase-1-dependent mitochondrial damage and block of mitophagy. Proc Natl Acad Sci USA. 2014;111(43):15514–9. doi: 10.1073/pnas.1414859111. DOI: https://doi.org/10.1073/pnas.1414859111
16. Diamond CE, Khameneh HJ, Brough D, et al. Novel perspectives on non-canonical inflammasome activation. Immunotargets Ther. 2015;4:131–41. doi: 10.2147/ITT.S57976. DOI: https://doi.org/10.2147/ITT.S57976
17. Lamkanfi M, Dixit VM. Modulation of inflammasome pathways by bacterial and viral pathogens. J Immunol. 2011;187(2):597–602. doi: 10.4049/jimmunol.1100229. DOI: https://doi.org/10.4049/jimmunol.1100229
18. Strowig T, Henao-Mejia J, Elinav E, et al. Inflammasomes in health and disease. Nature. 2012;481(7381):278–86. doi: 10.1038/nature10759. DOI: https://doi.org/10.1038/nature10759
19. Rashidi M, Simpson DS, Hempel A, et al. The Pyroptotic Cell Death Effector Gasdermin D Is Activated by Gout-Associated Uric Acid Crystals but Is Dispensable for Cell Death and IL-1β J Immunol. 2019;203(3):736–48. doi: 10.4049/jimmunol.1900228. DOI: https://doi.org/10.4049/jimmunol.1900228
20. Sahoo AK, Dandapat J, Dash UC, et al. Features and outcomes of drugs for combination therapy as multi-targets strategy to combat Alzheimer’s disease. J Ethnopharmacol. 2018;215:42–73. doi: 10.1016/j.jep.2017.12.015. DOI: https://doi.org/10.1016/j.jep.2017.12.015
21. Freeman LC, Ting JP. The pathogenic role of the inflammasome in neurodegenerative diseases. J Neurochem. 2016;136(Suppl 1):29–38. doi: 10.1111/jnc.13217. DOI: https://doi.org/10.1111/jnc.13217
22. Corrigan KL, Wall KC, Bartlett JA, et al. Cancer disparities in people with HIV: A systematic review of screening for non-AIDS-defining malignancies. 2019;125(6):843–53. doi: 10.1002/cncr.31838. DOI: https://doi.org/10.1002/cncr.31838
23. Doitsh G, Galloway NL, Geng X, et al. Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection. Nature. 2014;505(7484):509–14. doi: 10.1038/nature12940. DOI: https://doi.org/10.1038/nature12940
24. Monroe KM, Yang Z, Johnson JR, et al. IFI16 DNA sensor is required for death of lymphoid CD4 T cells abortively infected with HIV. Science. 2014;343(6169):428–32. doi: 10.1126/science.1243640. DOI: https://doi.org/10.1126/science.1243640
25. Wannamaker W, Davies R, Namchuk M, et al. VX-765, an orally available selective interleukin (IL)-converting enzyme/caspase-1 inhibitor, exhibits potent anti-inflammatory activities by inhibiting the release of IL-1beta and IL-18. J Pharmacol Exp Ther. 2007;321(2):509–16. doi: 10.1124/jpet.106.111344. DOI: https://doi.org/10.1124/jpet.106.111344
26. Asahchop EL, Meziane O, Mamik MK, et al. Reduced antiretroviral drug efficacy and concentration in HIV-infected microglia contributes to viral persistence in brain. Retrovirology. 2017;14(1):47. doi: 10.1186/s12977-017-0370-5. DOI: https://doi.org/10.1186/s12977-017-0370-5
27. Mamik MK, Hui E, Branton WG, et al. HIV-1 Viral Protein R Activates NLRP3 Inflammasome in Microglia: Implications for HIV-1 Associated Neuroinflammation. J Neuroimmune Pharmacol. 2017;12(2):233–48. doi: 10.1007/s11481-016-9708-3. DOI: https://doi.org/10.1007/s11481-016-9708-3
28. Vandanmagsar B, Youm Y, Ravussin A, et al. The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance. Nat Med. 2011;17(2):179–88. doi: 10.1038/nm.2279. DOI: https://doi.org/10.1038/nm.2279
29. Nagarajan K, Soundarapandian K, Thorne RF, et al. Activation of Pyroptotic Cell Death Pathways in Cancer: An Alternative Therapeutic Approach. Transl Oncol. 2019;12(7):925–31. doi: 10.1016/j.tranon.2019.04.010. DOI: https://doi.org/10.1016/j.tranon.2019.04.010
30. Luan J, Ju D. Inflammasome: A Double-Edged Sword in Liver Front Immunol. 2018;9:2201–9. doi: 10.3389/fimmu.2018.02201. DOI: https://doi.org/10.3389/fimmu.2018.02201
31. Chu Q, Jiang Y, Zhang W, et al. Pyroptosis is involved in the pathogenesis of human hepatocellular carcinoma. Oncotarget. 2016;7(51):84658–65. doi: 10.18632/oncotarget.12384. DOI: https://doi.org/10.18632/oncotarget.12384
32. Place DE, Kanneganti TD. Recent advances in inflammasome biology. Curr Opin Immunol. 2018;50:32–8. doi: 10.1016/j.coi.2017.10.011. DOI: https://doi.org/10.1016/j.coi.2017.10.011
33. Wang H, Luo Q, Feng X, et al. NLRP3 promotes tumor growth and metastasis in human oral squamous cell carcinoma. BMC Cancer. 2018;18(1):500–12. doi: 10.1186/s12885-018-4403-9. DOI: https://doi.org/10.1186/s12885-018-4403-9
34. Elion DL, Jacobson ME, Hicks DJ, et al. Therapeutically Active RIG-I Agonist Induces Immunogenic Tumor Cell Killing in Breast Cancer Res. 2018;78(21):6183–95. doi: 10.1158/0008-5472.can-18-0730. DOI: https://doi.org/10.1158/0008-5472.CAN-18-0730
35. Pizato N, Luzete BC, Kiffer LV, et al. Omega-3 docosahexaenoic acid induces pyroptosis cell death in triple-negative breast cancer cells. Sci Rep. 2018;8(1):1952–60. doi: 10.1038/s41598-018-20422-0. DOI: https://doi.org/10.1038/s41598-018-20422-0
36. Baranovskiy AG, Babayeva ND, Suwa Y, et al. Structural basis for inhibition of DNA replication by aphidicolin. Nucl Acids Res. 2014;42(22):14013–21. doi: 10.1093/nar/gku1209. DOI: https://doi.org/10.1093/nar/gku1209
37. Han T, Goralski M, Capota E, et al. The antitumor toxin CD437 is a direct inhibitor of DNA polymerase α. Nat Chem Biol. 2016;12(7):511–5. doi: 10.1038/nchembio.2082. DOI: https://doi.org/10.1038/nchembio.2082
38. Gutteridge RE, Ndiaye MA, Liu X, et al. Plk1 Inhibitors in Cancer Therapy: From Laboratory to Clinics. Mol Cancer 2016;15(7):1427–35. doi: 10.1158/1535-7163.mct-15-0897. DOI: https://doi.org/10.1158/1535-7163.MCT-15-0897
39. Liu X. Targeting Polo-Like Kinases: A Promising Therapeutic Approach for Cancer Transl Oncol. 2015;8(3):185–95. doi: 10.1016/j.tranon.2015.03.010. DOI: https://doi.org/10.1016/j.tranon.2015.03.010
40. Konjevic GM, Vuletic AM, Mirjacic Martinovic KM, et al. The role of cytokines in the regulation of NK cells in the tumor environment. Cytokine. 2019;117:30–40. doi: 10.1016/j.cyto.2019.02.001. DOI: https://doi.org/10.1016/j.cyto.2019.02.001
41. Nakanishi K. Unique Action of Interleukin-18 on T Cells and Other Immune Cells. Front Immunol. 2018;9:763. doi: 10.3389/fimmu.2018.00763. DOI: https://doi.org/10.3389/fimmu.2018.00763
42. Cao R, Farnebo J, Kurimoto M, et al. Interleukin-18 acts as an angiogenesis and tumor suppressor FASEB J. 1999;13(15):2195–202. doi: 10.1096/fasebj.13.15.2195. DOI: https://doi.org/10.1096/fasebj.13.15.2195
43. Li A, Yi M, Qin S, et al. Prospects for combining immune checkpoint blockade with PARP inhibition. J Hematol Oncol. 2019;12(1):98. doi: 10.1186/s13045-019-0784-8. DOI: https://doi.org/10.1186/s13045-019-0784-8