Staphylococcus Aureus Mediates Pyroptosis in Bovine Mammary Epithelial Cell Via Activation of NLRP3 Inflammasome

Overview

Journal Vet Res

Publisher Biomed Central

Specialty Veterinary Medicine

Date 2022 Feb 6

PMID 35123552

Authors

Xiaozhou Wang

Mingchao Liu

Na Geng

Yongzhen Du

Zhaoming Li

Xin Gao

Bo Han

Jianzhu Liu

Yongxia Liu

Affiliations

Soon will be listed here.

Abstract

Cell death and inflammation are intimately linked during mastitis due to Staphylococcus aureus (S. aureus). Pyroptosis, a programmed necrosis triggered by gasdermin protein family, often occurs after inflammatory caspase activation. Many pathogens invade host cells and activate cell-intrinsic death mechanisms, including pyroptosis, apoptosis, and necroptosis. We reported that bovine mammary epithelial cells (MAC-T) respond to S. aureus by NOD-like receptor protein 3 (NLRP3) inflammasome activation through K efflux, leading to the recruitment of apoptosis-associated speck-like protein (ASC) and the activation of caspase-1. The activated caspase-1 cleaves gasdermin D (GSDMD) and forms a N-terminal pore forming domain that drives swelling and membrane rupture. Membrane rupture results in the release of the pro-inflammatory cytokines IL-18 and IL-1β, which are activated by caspase-1. Can modulate GSDMD activation by NLRP3-dependent caspase-1 activation and then cause pyroptosis of bovine mammary epithelial cells.

Citing Articles

Saenz-de-Juano M, Silvestrelli G, Buri S, Zinsli L, Schmelcher M, Ulbrich S Sci Rep. 2025; 15(1):6059.

PMID: 39972051 PMC: 11840098. DOI: 10.1038/s41598-025-90466-6.

HCAR2 Modulates the Crosstalk between Mammary Epithelial Cells and Macrophages to Mitigate Staphylococcus aureus Infection in the Mouse Mammary Gland.

Ran X, Li K, Li Y, Guo W, Wang X, Guo W Adv Sci (Weinh). 2025; 12(9):e2411947.

PMID: 39792800 PMC: 11884543. DOI: 10.1002/advs.202411947.

Selenomethionine Mitigates Effects of Induced Inflammation, Oxidative Stress, and Apoptosis in Bovine Mammary Epithelial Cells.

Assabayev T, Han J, Bahetijiang H, Abdrassilova V, Khan M, Barkema H Int J Mol Sci. 2024; 25(20).

PMID: 39456758 PMC: 11507929. DOI: 10.3390/ijms252010976.

Modulatory Effects of Regulated Cell Death: An Innovative Preventive Approach for the Control of Mastitis.

Xia X, Ren P, Bai Y, Li J, Zhang H, Wang L Cells. 2024; 13(20.

PMID: 39451217 PMC: 11506078. DOI: 10.3390/cells13201699.

RACK1 and NEK7 mediate GSDMD-dependent macrophage pyroptosis upon Streptococcus suis infection.

Shen X, Ran J, Yang Q, Li B, Lu Y, Zheng J Vet Res. 2024; 55(1):120.

PMID: 39334337 PMC: 11428613. DOI: 10.1186/s13567-024-01376-w.

References

Zhao X, Lacasse P . Mammary tissue damage during bovine mastitis: causes and control. J Anim Sci. 2007; 86(13 Suppl):57-65. DOI: 10.2527/jas.2007-0302. View

Wang Y, Gao W, Shi X, Ding J, Liu W, He H . Chemotherapy drugs induce pyroptosis through caspase-3 cleavage of a gasdermin. Nature. 2017; 547(7661):99-103. DOI: 10.1038/nature22393. View

Boucher D, Monteleone M, Coll R, Chen K, Ross C, Teo J . Caspase-1 self-cleavage is an intrinsic mechanism to terminate inflammasome activity. J Exp Med. 2018; 215(3):827-840. PMC: 5839769. DOI: 10.1084/jem.20172222. View

Fernandes-Alnemri T, Wu J, Yu J, Datta P, Miller B, Jankowski W . The pyroptosome: a supramolecular assembly of ASC dimers mediating inflammatory cell death via caspase-1 activation. Cell Death Differ. 2007; 14(9):1590-604. PMC: 3345951. DOI: 10.1038/sj.cdd.4402194. View

LaRock C, Cookson B . Burning down the house: cellular actions during pyroptosis. PLoS Pathog. 2013; 9(12):e1003793. PMC: 3868505. DOI: 10.1371/journal.ppat.1003793. View

Shi J, Gao W, Shao F . Pyroptosis: Gasdermin-Mediated Programmed Necrotic Cell Death. Trends Biochem Sci. 2016; 42(4):245-254. DOI: 10.1016/j.tibs.2016.10.004. View

Gurung P, Lukens J, Kanneganti T . Mitochondria: diversity in the regulation of the NLRP3 inflammasome. Trends Mol Med. 2014; 21(3):193-201. PMC: 4352396. DOI: 10.1016/j.molmed.2014.11.008. View

Kayagaki N, Stowe I, Lee B, ORourke K, Anderson K, Warming S . Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling. Nature. 2015; 526(7575):666-71. DOI: 10.1038/nature15541. View

Anderson K, Lyman R, Moury K, Ray D, Watson D, Correa M . Molecular epidemiology of Staphylococcus aureus mastitis in dairy heifers. J Dairy Sci. 2012; 95(9):4921-4930. DOI: 10.3168/jds.2011-4913. View

10.

Haneklaus M, ONeill L . NLRP3 at the interface of metabolism and inflammation. Immunol Rev. 2015; 265(1):53-62. DOI: 10.1111/imr.12285. View

11.

Shi J, Zhao Y, Wang K, Shi X, Wang Y, Huang H . Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death. Nature. 2015; 526(7575):660-5. DOI: 10.1038/nature15514. View

12.

Ding J, Wang K, Liu W, She Y, Sun Q, Shi J . Pore-forming activity and structural autoinhibition of the gasdermin family. Nature. 2016; 535(7610):111-6. DOI: 10.1038/nature18590. View

13.

Wang K, Sun Q, Zhong X, Zeng M, Zeng H, Shi X . Structural Mechanism for GSDMD Targeting by Autoprocessed Caspases in Pyroptosis. Cell. 2020; 180(5):941-955.e20. DOI: 10.1016/j.cell.2020.02.002. View

14.

Dego O, van Dijk J, Nederbragt H . Factors involved in the early pathogenesis of bovine Staphylococcus aureus mastitis with emphasis on bacterial adhesion and invasion. A review. Vet Q. 2003; 24(4):181-98. DOI: 10.1080/01652176.2002.9695135. View

15.

Frank D, Vince J . Pyroptosis versus necroptosis: similarities, differences, and crosstalk. Cell Death Differ. 2018; 26(1):99-114. PMC: 6294779. DOI: 10.1038/s41418-018-0212-6. View

16.

Prochnicki T, Latz E . Inflammasomes on the Crossroads of Innate Immune Recognition and Metabolic Control. Cell Metab. 2017; 26(1):71-93. DOI: 10.1016/j.cmet.2017.06.018. View

17.

Man S, Karki R, Kanneganti T . Molecular mechanisms and functions of pyroptosis, inflammatory caspases and inflammasomes in infectious diseases. Immunol Rev. 2017; 277(1):61-75. PMC: 5416822. DOI: 10.1111/imr.12534. View

18.

Campden R, Zhang Y . The role of lysosomal cysteine cathepsins in NLRP3 inflammasome activation. Arch Biochem Biophys. 2019; 670:32-42. DOI: 10.1016/j.abb.2019.02.015. View

19.

Broz P, Pelegrin P, Shao F . The gasdermins, a protein family executing cell death and inflammation. Nat Rev Immunol. 2019; 20(3):143-157. DOI: 10.1038/s41577-019-0228-2. View

20.

Tang D, Kang R, Vanden Berghe T, Vandenabeele P, Kroemer G . The molecular machinery of regulated cell death. Cell Res. 2019; 29(5):347-364. PMC: 6796845. DOI: 10.1038/s41422-019-0164-5. View