细胞焦亡在呼吸道病毒感染脓毒症中的研究进展_Chinese Journal of Respiratory and Critical Care Medicine

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伍少多 ¹ , 张逸丹 ¹ ,  李筱妍 ²

1. ;
2. ;

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李筱妍, Email: 2415960869@qq.com

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DOI：

10.7507/1671-6205.202403003

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Citation： 伍少多, 张逸丹, 李筱妍. 细胞焦亡在呼吸道病毒感染脓毒症中的研究进展. Chinese Journal of Respiratory and Critical Care Medicine, 2025, 24(3): 225-228. doi: 10.7507/1671-6205.202403003 Copy

1.	Evans L, Rhodes A, Alhazzani W, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. Crit Care Med, 2021, 49(11): e1063-e1143.
2.	Karakike E, Giamarellos-Bourboulis EJ, Kyprianou M, et al. Coronavirus disease 2019 as cause of viral sepsis: a systematic review and meta-analysis. Crit Care Med, 2021, 49(12): 2042-2057.
3.	Gu X, Zhou F, Wang Y, et al. Respiratory viral sepsis: epidemiology, pathophysiology, diagnosis and treatment. Eur Respir Rev, 2020, 29(157): 200038.
4.	Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet, 2020, 395(10229): 1054-1062.
5.	Feng Y, Li M, Yangzhong X, et al. Pyroptosis in inflammation-related respiratory disease. J Physiol Biochem, 2022, 78(4): 721-737.
6.	Vora SM, Lieberman J, Wu H. Inflammasome activation at the crux of severe COVID-19. Nat Rev Immunol, 2021, 21(11): 694-703.
7.	Yap JKY, Moriyama M, Iwasaki A. Inflammasomes and pyroptosis as therapeutic targets for COVID-19. J Immunol, 2020, 205(2): 307-312.
8.	Rodrigues TS, De Sá KSG, Ishimoto A, et al. Inflammasomes are activated in response to SARS-CoV-2 infection and are associated with COVID-19 severity in patients. J Exp Med, 2021, 218(3): e20201707.
9.	Xu Q, Yang Y, Zhang X, et al. Association of pyroptosis and severeness of COVID-19 as revealed by integrated single-cell transcriptome data analysis. Immunoinformatics (Amst), 2022, 6: 100013.
10.	徐逸天, 曹彬. 病毒性感染中毒症—一个亟待重视的概念. 中华结核和呼吸杂志, 2021, 44(7): 674-679.
11.	Li H, Liu L, Zhang D, et al. SARS-CoV-2 and viral sepsis: observations and hypotheses. Lancet, 2020, 395(10235): 1517-1520.
12.	Coronaviridae Study Group of the International Committee on Taxonomy of Viruses, Gorbalenya AE, Baker SC, et al. The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat Microbiol, 2020, 5(4): 536-544.
13.	Harrison AG, Lin T, Wang P. Mechanisms of SARS-CoV-2 transmission and pathogenesis. Trends Immunol, 2020, 41(12): 1100-1115.
14.	Ragab D, Salah Eldin H, Taeimah M, et al. The COVID-19 cytokine storm; what we know so far. Front Immunol, 2020, 11: 1446.
15.	Chen G, Wu D, Guo W, et al. Clinical and immunological features of severe and moderate coronavirus disease 2019. J Clin Invest, 2020, 130(5): 2620-2629.
16.	Gao Y, Li T, Han M, et al. Diagnostic utility of clinical laboratory data determinations for patients with the severe COVID‐19. J Med Virol, 2020, 92(7): 791-796.
17.	McGonagle D, Sharif K, O’Regan A, et al. The role of cytokines including interleukin-6 in COVID-19 induced pneumonia and macrophage activation syndrome-like disease. Autoimmun Rev, 2020, 19(6): 102537.
18.	Guan W, Ni Z, Hu Y, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med, 2020, 382(18): 1708-1720.
19.	Kuriakose T, Kanneganti TD. “Pyroptosis in Antiviral Immunity. ” In: Mocarski ES, Mandal P, editors. Alternate Programmed Cell Death Signaling in Antiviral Host Defense. Current Topics in Microbiology and Immunology. Cham: Springer International Publishing (2019), 65-83.
20.	Ding J, Wang K, Liu W, et al. Pore-forming activity and structural autoinhibition of the gasdermin family. Nature, 2016, 535(7610): 111-116.
21.	Rao Z, Zhu Y, Yang P, et al. Pyroptosis in inflammatory diseases and cancer. Theranostics, 2022, 12(9): 4310-4329.
22.	Kayagaki N, Stowe IB, Lee BL, et al. Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling. Nature, 2015, 526(7575): 666-671.
23.	Tan Y, Chen Q, Li X, et al. Pyroptosis: a new paradigm of cell death for fighting against cancer. J Exp Clin Cancer Res, 2021, 40(1): 153.
24.	Miao EA, Leaf IA, Treuting PM, et al. Caspase-1-induced pyroptosis is an innate immune effector mechanism against intracellular bacteria. Nat Immunol, 2010, 11(12): 1136-1142.
25.	Sharma AK, Ismail N. Non-canonical inflammasome pathway: the role of cell death and inflammation in ehrlichiosis. Cells, 2023, 12(22): 2597.
26.	Shi J, Zhao Y, Wang Y, et al. Inflammatory caspases are innate immune receptors for intracellular LPS. Nature, 2014, 514(7521): 187-192.
27.	Zanoni I, Tan Y, Di Gioia M, et al. An endogenous caspase-11 ligand elicits interleukin-1 release from living dendritic cells. Science, 2016, 352(6290): 1232-1236.
28.	Yang F, Bettadapura SN, Smeltzer MS, et al. Pyroptosis and pyroptosis-inducing cancer drugs. Acta Pharmacol Sin, 2022, 43(10): 2462-2473.
29.	Jiao C, Zhang H, Li H, et al. Caspase-3/GSDME mediated pyroptosis: a potential pathway for sepsis. Int Immunopharmacol, 2023, 124(Pt B): 111022.
30.	Tsuchiya K. Switching from apoptosis to pyroptosis: gasdermin-elicited inflammation and antitumor immunity. Int J Mol Sci, 2021, 22(1): 426.
31.	Zhou Z, He H, Wang K, et al. Granzyme A from cytotoxic lymphocytes cleaves GSDMB to trigger pyroptosis in target cells. Science, 2020, 368(6494): eaaz7548.
32.	Liu Y, Fang Y, Chen X, et al. Gasdermin E-mediated target cell pyroptosis by CAR T cells triggers cytokine release syndrome. Sci Immunol, 2020, 5(43): eaax7969.
33.	Papayannopoulos V, Metzler KD, Hakkim A, et al. Neutrophil elastase and myeloperoxidase regulate the formation of neutrophil extracellular traps. J Cell Biol, 2010, 191(3): 677-691.
34.	Brinkmann V, Reichard U, Goosmann C, et al. Neutrophil extracellular traps kill bacteria. Science, 2004, 303(5663): 1532-1535.
35.	Zhu C, Wang Y, Liu Q, et al. Dysregulation of neutrophil death in sepsis. Front Immunol, 2022, 13: 963955.
36.	Dubyak GR, Miller BA, Pearlman E. Pyroptosis in neutrophils: Multimodal integration of inflammasome and regulated cell death signaling pathways. Immunol Rev, 2023, 314(1): 229-249.
37.	Zhu Y, Chen X, Liu X. NETosis and neutrophil extracellular traps in COVID-19: immunothrombosis and beyond. Front Immunol, 2022, 13: 838011.
38.	Becker K, Beythien G, de Buhr N, et al. Vasculitis and neutrophil extracellular traps in lungs of golden Syrian hamsters with SARS-CoV-2. Front Immunol, 2021, 12: 640842.
39.	Al-Kuraishy HM, Al-Gareeb AI, Al-hussaniy HA, et al. Neutrophil extracellular traps (NETs) and Covid-19: a new frontiers for therapeutic modality. Int Immunopharmacol, 2022, 104: 108516.
40.	Veras FP, Pontelli MC, Silva CM, et al. SARS-CoV-2–triggered neutrophil extracellular traps mediate COVID-19 pathology. J Exp Med, 2020, 217(12): e20201129.
41.	Wu C, Lu W, Zhang Y, et al. Inflammasome activation triggers blood clotting and host death through pyroptosis. Immunity, 2019, 50(6): 1401-1411,e4.
42.	Gando S, Levi M, Toh CH. Disseminated intravascular coagulation. Nat Rev Dis Primers, 2016, 2(1): 16037.
43.	Grover SP, Mackman N. Tissue factor: an essential mediator of hemostasis and trigger of thrombosis. Arterioscler Thromb Vasc Biol, 2018, 38(4): 709-725.
44.	Iba T, Levy JH, Levi M, et al. Coagulopathy in COVID‐19. J Thromb Haemost, 2020, 18(9): 2103-2109.
45.	Skendros P, Mitsios A, Chrysanthopoulou A, et al. Complement and tissue factor-enriched neutrophil extracellular traps are key drivers in COVID-19 immunothrombosis. J Clin Invest, 2020, 130(11): 6151-6157.
46.	Levi M, Thachil J, Iba T, et al. Coagulation abnormalities and thrombosis in patients with COVID-19. Lancet Haematol, 2020, 7(6): e438-e440.
47.	张连芳, 谢榕城, 林雪烽, 等. 重症监护室内重症肺炎患者新发血栓事件和病死率的研究分析. 中国呼吸与危重监护杂志, 2024, 23(1): 7-14.
48.	Connors JM, Levy JH. COVID-19 and its implications for thrombosis and anticoagulation. Blood, 2020, 135(23): 2033-2040.
49.	Man SM. Inflammasomes in the gastrointestinal tract: infection, cancer and gut microbiota homeostasis. Nat Rev Gastroenterol Hepatol, 2018, 15(12): 721-737.
50.	Yeoh YK, Zuo T, Lui GCY, et al. Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19. Gut, 2021, 70(4): 698-706.
51.	Frank D, Vince JE. Pyroptosis versus necroptosis: similarities, differences, and crosstalk. Cell Death Differ, 2019, 26(1): 99-114.
52.	Lucas C, Wong P, Klein J, et al. Longitudinal analyses reveal immunological misfiring in severe COVID-19. Nature, 2020, 584(7821): 463-469.
53.	Hantoushzadeh S, Norooznezhad AH. Possible cause of inflammatory storm and septic shock in patients diagnosed with (COVID-19). Arch Med Res, 2020, 51(4): 347-348.
54.	李俏琦, 杨茜, 高玲, 等. 细胞因子风暴与病毒性肺炎. 中国呼吸与危重监护杂志, 2021, 20(1): 70-75.

1. Evans L, Rhodes A, Alhazzani W, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. Crit Care Med, 2021, 49(11): e1063-e1143.
2. Karakike E, Giamarellos-Bourboulis EJ, Kyprianou M, et al. Coronavirus disease 2019 as cause of viral sepsis: a systematic review and meta-analysis. Crit Care Med, 2021, 49(12): 2042-2057.
3. Gu X, Zhou F, Wang Y, et al. Respiratory viral sepsis: epidemiology, pathophysiology, diagnosis and treatment. Eur Respir Rev, 2020, 29(157): 200038.
4. Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet, 2020, 395(10229): 1054-1062.
5. Feng Y, Li M, Yangzhong X, et al. Pyroptosis in inflammation-related respiratory disease. J Physiol Biochem, 2022, 78(4): 721-737.
6. Vora SM, Lieberman J, Wu H. Inflammasome activation at the crux of severe COVID-19. Nat Rev Immunol, 2021, 21(11): 694-703.
7. Yap JKY, Moriyama M, Iwasaki A. Inflammasomes and pyroptosis as therapeutic targets for COVID-19. J Immunol, 2020, 205(2): 307-312.
8. Rodrigues TS, De Sá KSG, Ishimoto A, et al. Inflammasomes are activated in response to SARS-CoV-2 infection and are associated with COVID-19 severity in patients. J Exp Med, 2021, 218(3): e20201707.
9. Xu Q, Yang Y, Zhang X, et al. Association of pyroptosis and severeness of COVID-19 as revealed by integrated single-cell transcriptome data analysis. Immunoinformatics (Amst), 2022, 6: 100013.
10. 徐逸天, 曹彬. 病毒性感染中毒症—一个亟待重视的概念. 中华结核和呼吸杂志, 2021, 44(7): 674-679.
11. Li H, Liu L, Zhang D, et al. SARS-CoV-2 and viral sepsis: observations and hypotheses. Lancet, 2020, 395(10235): 1517-1520.
12. Coronaviridae Study Group of the International Committee on Taxonomy of Viruses, Gorbalenya AE, Baker SC, et al. The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat Microbiol, 2020, 5(4): 536-544.
13. Harrison AG, Lin T, Wang P. Mechanisms of SARS-CoV-2 transmission and pathogenesis. Trends Immunol, 2020, 41(12): 1100-1115.
14. Ragab D, Salah Eldin H, Taeimah M, et al. The COVID-19 cytokine storm; what we know so far. Front Immunol, 2020, 11: 1446.
15. Chen G, Wu D, Guo W, et al. Clinical and immunological features of severe and moderate coronavirus disease 2019. J Clin Invest, 2020, 130(5): 2620-2629.
16. Gao Y, Li T, Han M, et al. Diagnostic utility of clinical laboratory data determinations for patients with the severe COVID‐19. J Med Virol, 2020, 92(7): 791-796.
17. McGonagle D, Sharif K, O’Regan A, et al. The role of cytokines including interleukin-6 in COVID-19 induced pneumonia and macrophage activation syndrome-like disease. Autoimmun Rev, 2020, 19(6): 102537.
18. Guan W, Ni Z, Hu Y, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med, 2020, 382(18): 1708-1720.
19. Kuriakose T, Kanneganti TD. “Pyroptosis in Antiviral Immunity. ” In: Mocarski ES, Mandal P, editors. Alternate Programmed Cell Death Signaling in Antiviral Host Defense. Current Topics in Microbiology and Immunology. Cham: Springer International Publishing (2019), 65-83.
20. Ding J, Wang K, Liu W, et al. Pore-forming activity and structural autoinhibition of the gasdermin family. Nature, 2016, 535(7610): 111-116.
21. Rao Z, Zhu Y, Yang P, et al. Pyroptosis in inflammatory diseases and cancer. Theranostics, 2022, 12(9): 4310-4329.
22. Kayagaki N, Stowe IB, Lee BL, et al. Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling. Nature, 2015, 526(7575): 666-671.
23. Tan Y, Chen Q, Li X, et al. Pyroptosis: a new paradigm of cell death for fighting against cancer. J Exp Clin Cancer Res, 2021, 40(1): 153.
24. Miao EA, Leaf IA, Treuting PM, et al. Caspase-1-induced pyroptosis is an innate immune effector mechanism against intracellular bacteria. Nat Immunol, 2010, 11(12): 1136-1142.
25. Sharma AK, Ismail N. Non-canonical inflammasome pathway: the role of cell death and inflammation in ehrlichiosis. Cells, 2023, 12(22): 2597.
26. Shi J, Zhao Y, Wang Y, et al. Inflammatory caspases are innate immune receptors for intracellular LPS. Nature, 2014, 514(7521): 187-192.
27. Zanoni I, Tan Y, Di Gioia M, et al. An endogenous caspase-11 ligand elicits interleukin-1 release from living dendritic cells. Science, 2016, 352(6290): 1232-1236.
28. Yang F, Bettadapura SN, Smeltzer MS, et al. Pyroptosis and pyroptosis-inducing cancer drugs. Acta Pharmacol Sin, 2022, 43(10): 2462-2473.
29. Jiao C, Zhang H, Li H, et al. Caspase-3/GSDME mediated pyroptosis: a potential pathway for sepsis. Int Immunopharmacol, 2023, 124(Pt B): 111022.
30. Tsuchiya K. Switching from apoptosis to pyroptosis: gasdermin-elicited inflammation and antitumor immunity. Int J Mol Sci, 2021, 22(1): 426.
31. Zhou Z, He H, Wang K, et al. Granzyme A from cytotoxic lymphocytes cleaves GSDMB to trigger pyroptosis in target cells. Science, 2020, 368(6494): eaaz7548.
32. Liu Y, Fang Y, Chen X, et al. Gasdermin E-mediated target cell pyroptosis by CAR T cells triggers cytokine release syndrome. Sci Immunol, 2020, 5(43): eaax7969.
33. Papayannopoulos V, Metzler KD, Hakkim A, et al. Neutrophil elastase and myeloperoxidase regulate the formation of neutrophil extracellular traps. J Cell Biol, 2010, 191(3): 677-691.
34. Brinkmann V, Reichard U, Goosmann C, et al. Neutrophil extracellular traps kill bacteria. Science, 2004, 303(5663): 1532-1535.
35. Zhu C, Wang Y, Liu Q, et al. Dysregulation of neutrophil death in sepsis. Front Immunol, 2022, 13: 963955.
36. Dubyak GR, Miller BA, Pearlman E. Pyroptosis in neutrophils: Multimodal integration of inflammasome and regulated cell death signaling pathways. Immunol Rev, 2023, 314(1): 229-249.
37. Zhu Y, Chen X, Liu X. NETosis and neutrophil extracellular traps in COVID-19: immunothrombosis and beyond. Front Immunol, 2022, 13: 838011.
38. Becker K, Beythien G, de Buhr N, et al. Vasculitis and neutrophil extracellular traps in lungs of golden Syrian hamsters with SARS-CoV-2. Front Immunol, 2021, 12: 640842.
39. Al-Kuraishy HM, Al-Gareeb AI, Al-hussaniy HA, et al. Neutrophil extracellular traps (NETs) and Covid-19: a new frontiers for therapeutic modality. Int Immunopharmacol, 2022, 104: 108516.
40. Veras FP, Pontelli MC, Silva CM, et al. SARS-CoV-2–triggered neutrophil extracellular traps mediate COVID-19 pathology. J Exp Med, 2020, 217(12): e20201129.
41. Wu C, Lu W, Zhang Y, et al. Inflammasome activation triggers blood clotting and host death through pyroptosis. Immunity, 2019, 50(6): 1401-1411,e4.
42. Gando S, Levi M, Toh CH. Disseminated intravascular coagulation. Nat Rev Dis Primers, 2016, 2(1): 16037.
43. Grover SP, Mackman N. Tissue factor: an essential mediator of hemostasis and trigger of thrombosis. Arterioscler Thromb Vasc Biol, 2018, 38(4): 709-725.
44. Iba T, Levy JH, Levi M, et al. Coagulopathy in COVID‐19. J Thromb Haemost, 2020, 18(9): 2103-2109.
45. Skendros P, Mitsios A, Chrysanthopoulou A, et al. Complement and tissue factor-enriched neutrophil extracellular traps are key drivers in COVID-19 immunothrombosis. J Clin Invest, 2020, 130(11): 6151-6157.
46. Levi M, Thachil J, Iba T, et al. Coagulation abnormalities and thrombosis in patients with COVID-19. Lancet Haematol, 2020, 7(6): e438-e440.
47. 张连芳, 谢榕城, 林雪烽, 等. 重症监护室内重症肺炎患者新发血栓事件和病死率的研究分析. 中国呼吸与危重监护杂志, 2024, 23(1): 7-14.
48. Connors JM, Levy JH. COVID-19 and its implications for thrombosis and anticoagulation. Blood, 2020, 135(23): 2033-2040.
49. Man SM. Inflammasomes in the gastrointestinal tract: infection, cancer and gut microbiota homeostasis. Nat Rev Gastroenterol Hepatol, 2018, 15(12): 721-737.
50. Yeoh YK, Zuo T, Lui GCY, et al. Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19. Gut, 2021, 70(4): 698-706.
51. Frank D, Vince JE. Pyroptosis versus necroptosis: similarities, differences, and crosstalk. Cell Death Differ, 2019, 26(1): 99-114.
52. Lucas C, Wong P, Klein J, et al. Longitudinal analyses reveal immunological misfiring in severe COVID-19. Nature, 2020, 584(7821): 463-469.
53. Hantoushzadeh S, Norooznezhad AH. Possible cause of inflammatory storm and septic shock in patients diagnosed with (COVID-19). Arch Med Res, 2020, 51(4): 347-348.
54. 李俏琦, 杨茜, 高玲, 等. 细胞因子风暴与病毒性肺炎. 中国呼吸与危重监护杂志, 2021, 20(1): 70-75.

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细胞焦亡在呼吸道病毒感染脓毒症中的研究进展

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