ARTICLE
Volume 10,Issue 7
10 March 2025
Research Progress on the Mechanism of GSDMDInduced Pyroptosis in Macrophages
Zhaoru Wu ,
Chengxin Lv ,
Feixiang Huang ,
Jiedan Liao
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1
College of Animal Science and Technology, Foshan University, Foshan 528225, Guangdong Province, China,
2
Henan Animal Health Supervision Institute, Zhengzhou 450000, Henan Province, China,
JCNR 2025 , 9(2), 79–84;
https://doi.org/10.26689/jcnr.v9i2.9831
© 2025 by the Authors. Licensee Whioce Publishing, Singapore. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Abstract
Pyroptosis is a form of programmed cell death. Excessive or uncontrolled pyroptosis and the production of pro-inflammatory cytokines can lead to organ damage, circulatory failure, and even death. Gasdermin D (GSDMD) is the primary executor of pyroptosis in macrophages. Upon cleavage, the N-terminal domain of GSDMD (GSDMD-N) is activated and oligomerizes to form pore-like structures in the plasma membrane, triggering pyroptosis and resulting in the release of pro-inflammatory cytokines such as interleukin-1β (IL-1β). As a key executioner molecule of pyroptosis, Gasdermin D plays a crucial role in pathogen-induced pyroptosis in macrophages. With in-depth research on the function and regulatory mechanisms of GSDMD, its role in pathogen-induced macrophage pyroptosis has gradually been revealed. This article elaborates on the mechanism of GSDMD in pathogen-induced macrophage pyroptosis, providing insights for exploring pyroptosis in the prevention and control of bacterial diseases, and identifying new therapeutic targets for bacterial infections.
References
Broz P, Pelegrin P, Shao F, 2020, The Gasdermins, a Protein Family Executing Cell Death and Inflammation. Nat Rev Immunol, 20(3): 143–157.
Wright SS, Kumari P, Fraile-Agreda V, et al., 2025, Transplantation of Gasdermin Pores by Extracellular Vesicles Propagates Pyroptosis to Bystander Cells. Cell, 188(2): 280–291.
Shi J, Gao W, Shao F, 2017, Pyroptosis: Gasdermin-Mediated Programmed Necrotic Cell Death. Trends Biochem Sci, 42(4): 245–254.
Ni L, Chen D, Zhao Y, et al., 2024, Unveiling the Flames: Macrophage Pyroptosis and Its Crucial Role in Liver Diseases. Front Immunol, 15: 1338125.
Labbe K, Saleh M, 2008, Cell Death in the Host Response to Infection. Cell Death Differ, 15(9): 1339–1349.
Gou X, Xu W, Liu Y, et al., 2022, IL-6 Prevents Lung Macrophage Death and Lung Inflammation Injury by Inhibiting GSDME- and GSDMD-Mediated Pyroptosis during Pneumococcal Pneumosepsis. Microbiol Spectr, 10(2): e204921.
Qu Z, Zhou J, Zhou Y, et al., 2020, Mycobacterial EST12 Activates a RACK1-NLRP3-Gasdermin D Pyroptosis-IL-1β Immune Pathway. Sci Adv, 6(43): 1–18.
Pandeya A, Zhang Y, Cui J, et al., 2023, Inflammasome Activation and Pyroptosis Mediate Coagulopathy and Inflammation in Salmonella Systemic Infection. Microbiol Res, 275: 127460.
Mehrotra P, Maschalidi S, Boeckaerts L, et al., 2024, Oxylipins and Metabolites from Pyroptotic Cells Act as Promoters of Tissue Repair. Nature, 631(8019): 207–215.
Wei Y, Lan B, Zheng T, et al., 2023, GSDME-Mediated Pyroptosis Promotes the Progression and Associated Inflammation of Atherosclerosis. Nat Commun, 14(1): 929.
He W, Wan H, Hu L, et al., 2015, Gasdermin D is an Executor of Pyroptosis and Required for Interleukin-1β Secretion. Cell Research, 25(12): 1285–1298.
Shi J, Zhao Y, Wang K, et al., 2015, Cleavage of GSDMD by Inflammatory Caspases Determines Pyroptotic Cell Death. Nature, 526(7575): 660–665.
Volchuk A, Ye A, Chi L, et al., 2020, Indirect Regulation of HMGB1 Release by Gasdermin D. Nat Commun, 11(1): 4561.
Galluzzi L, Vitale I, Aaronson SA, et al., 2018, Molecular Mechanisms of Cell Death: Recommendations of the Nomenclature Committee on Cell Death 2018. Cell Death Differ, 25(3): 486–541.
Liu X, Zhang Z, Ruan J, et al., 2016, Inflammasome-Activated Gasdermin D Causes Pyroptosis by Forming Membrane Pores. Nature, 535(7610): 153–158.
Cerqueira DM, Gomes M, Silva A, et al., 2018, Guanylate-Binding Protein 5 Licenses Caspase-11 for Gasdermin-D Mediated Host Resistance to Brucella Abortus Infection. PLoS Pathog, 14(12): e1007519.
Goncalves AV, Margolis SR, Quirino G, et al., 2019, Gasdermin-D and Caspase-7 are the Key Caspase-1/8 Substrates Downstream of the NAIP5/NLRC4 Inflammasome Required for Restriction of Legionella pneumophila. PLoS Pathog, 15(6): e1007886.
Wang J, Deobald K, Re F, 2019, Gasdermin D Protects from Melioidosis through Pyroptosis and Direct Killing of Bacteria. J Immunol, 202(12): 3468–3473.
Banerjee I, Behl B, Mendonca M, et al., 2018, Gasdermin D Restrains Type I Interferon Response to Cytosolic DNA by Disrupting Ionic Homeostasis. Immunity, 49(3): 413–426.
Kang R, Zeng L, Zhu S, et al., 2018, Lipid Peroxidation Drives Gasdermin D-Mediated Pyroptosis in Lethal Polymicrobial Sepsis. Cell Host Microbe, 24(1): 97–108.
Zheng M, Karki R, Kancharana B, et al., 2021, Caspase-6 Promotes Activation of the Caspase-11-NLRP3 Inflammasome during Gram-Negative Bacterial Infections. J Biol Chem, 297(6): 101379.
Man SM, Karki R, Kanneganti TD, 2017, Molecular Mechanisms and Functions of Pyroptosis, Inflammatory Caspases and Inflammasomes in Infectious Diseases. Immunol Rev, 277(1): 61–75.
Cheng CK, Yi M, Wang L, et al., 2024, Role of Gasdermin D in Inflammatory Diseases: From Mechanism to Therapeutics. Front Immunol, 15: 1456244.
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