Research progress of ferroptosis in pulmonary tuberculosis_West China Medical Journal

Authors：

HU Xiaojuan ,  YAN Fang , MANGUNU ShiNaBieKe , YU Minjie

Respiratory and respiratory Critical Care Center, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830000, P. R. China;

Corresponding author：

YAN Fang, Email: 58078817@qq.com

Keywords：

Ferroptosis; pulmonary tuberculosis; signal pathway; biomarkers

DOI：

10.7507/1002-0179.202407017

Video：

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Ferroptosis is a unique way of cell death discovered in recent years, which involves the lethal process of iron ion accumulation and lipid peroxidation, which is obviously different from the traditional cell death pathway such as apoptosis and necrosis. For a long time, tuberculosis has been a major infectious disease in the field of global public health, which brings a serious burden to the society because of its high morbidity and mortality. The emergence of drug resistance aggravates the difficulty of treating tuberculosis, and new treatment strategies and drug targets are urgently needed. Combined with the latest research progress at home and abroad, This article will discuss the molecular mechanism of ferroptosis and pulmonary tuberculosis and the relationship between signal pathways, biomarkers and related genes, in order to provide a new perspective for the diagnosis and treatment of pulmonary tuberculosis.

Citation： HU Xiaojuan, YAN Fang, MANGUNU ShiNaBieKe, YU Minjie. Research progress of ferroptosis in pulmonary tuberculosis. West China Medical Journal, 2025, 40(1): 132-135. doi: 10.7507/1002-0179.202407017 Copy

1.	World Health Organization. WHO TB knowledge sharing platform. Geneva: World Health Organization, 2023.
2.	Jiang X, Stockwell BR, Conrad M. Ferroptosis: mechanisms, biology and role in disease. Nat Rev Mol Cell Biol, 2021, 22(4): 266-282.
3.	Chen X, Li J, Kang R, et al. Ferroptosis: machinery and regulation. Autophagy, 2021, 17(9): 2054-2081.
4.	Amaral EP, Costa DL, Namasivayam S, et al. A major role for ferroptosis in Mycobacterium tuberculosis-induced cell death and tissue necrosis. J Exp Med, 2019, 216(3): 556-570.
5.	Yan R, Xie E, Li Y, et al. The structure of erastin-bound xCT-4F2hc complex reveals molecular mechanisms underlying erastin-induced ferroptosis. Cell Res, 2022, 32(7): 687-690.
6.	Chen H, Qi Q, Wu N, et al. Aspirin promotes RSL3-induced ferroptosis by suppressing mTOR/SREBP-1/SCD1-mediated lipogenesis in PIK3CA-mutant colorectal cancer. Redox Biol, 2022, 55: 102426.
7.	Dixon SJ, Lemberg KM, Lamprecht MR, et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell, 2012, 149(5): 1060-1072.
8.	Lin Z, Liu J, Long F, et al. The lipid flippase SLC47A1 blocks metabolic vulnerability to ferroptosis. Nat Commun, 2022, 13(1): 7965.
9.	Li C, Zhang Y, Liu J, et al. Mitochondrial DNA stress triggers autophagy-dependent ferroptotic death. Autophagy, 2021, 17(4): 948-960.
10.	Lee H, Zandkarimi F, Zhang Y, et al. Energy-stress-mediated AMPK activation inhibits ferroptosis. Nat Cell Biol, 2020, 22(2): 225-234.
11.	Sang M, Luo R, Bai Y, et al. Mitochondrial membrane anchored photosensitive nano-device for lipid hydroperoxides burst and inducing ferroptosis to surmount therapy-resistant cancer. Theranostics, 2019, 9(21): 6209-6223.
12.	Dorman SE, Schumacher SG, Alland D, et al. Xpert MTB/RIF ultra for detection of Mycobacterium tuberculosis and rifampicin resistance: a prospective multicentre diagnostic accuracy study. Lancet Infect Dis, 2018, 18(1): 76-84.
13.	Trébucq A, Enarson DA, Chiang CY, et al. Xpert^® MTB/RIF for national tuberculosis programmes in low-income countries: when, where and how?. Int J Tuberc Lung Dis, 2011, 15(12): 1567-1572.
14.	Amaral EP, Foreman TW, Namasivayam S, et al. GPX4 regulates cellular necrosis and host resistance in Mycobacterium tuberculosis infection. J Exp Med, 2022, 219(11): e20220504.
15.	Qiang L, Zhang Y, Lei Z, et al. A mycobacterial effector promotes ferroptosis-dependent pathogenicity and dissemination. Nat Commun, 2023, 14(1): 1430.
16.	Kassovska-Bratinova S, Yang G, Igarashi K, et al. Bach1 modulates heme oxygenase-1 expression in the neonatal mouse lung. Pediatr Res, 2009, 65(2): 145-149.
17.	Yamada N, Yamaya M, Okinaga S, et al. Microsatellite polymorphism in the heme oxygenase-1 gene promoter is associated with susceptibility to emphysema. Am J Hum Genet, 2000, 66(1): 187-195.
18.	Abdalla MY, Ahmad IM, Switzer B, et al. Induction of heme oxygenase-1 contributes to survival of Mycobacterium abscessus in human macrophages-like THP-1 cells. Redox Biol, 2015, 4: 328-339.
19.	Costa DL, Namasivayam S, Amaral EP, et al. Pharmacological inhibition of host heme oxygenase-1 suppresses Mycobacterium tuberculosis infection in vivo by a mechanism dependent on tlymphocytes. mBio, 2016, 7(5): e01675-16.
20.	Scharn CR, Collins AC, Nair VR, et al. Heme oxygenase-1 regulates inflammation and mycobacterial survival in human macrophages during Mycobacterium tuberculosis infection. J Immunol, 2016, 196(11): 4641-4649.
21.	Andrade BB, Pavan Kumar N, Mayer-Barber KD, et al. Plasma heme oxygenase-1 levels distinguish latent or successfully treated human tuberculosis from active disease. PLoS One, 2013, 8(5): e62618.
22.	Andrade BB, Pavan Kumar N, Amaral EP, et al. Heme oxygenase-1 regulation of matrix metalloproteinase-1 expression underlies distinct disease profiles in Tuberculosis. J Immunol, 2015, 195(6): 2763-2773.
23.	Reddy VP, Chinta KC, Saini V, et al. Ferritin H deficiency in myeloid compartments dysregulates host energy metabolism and increases susceptibility to Mycobacterium tuberculosis infection. Front Immunol, 2018, 9: 860.
24.	Yang S, Ouyang J, Lu Y, et al. A dual role of heme oxygenase-1 in tuberculosis. Front Immunol, 2022, 13: 842858.
25.	Xiao L, Huang H, Fan S, et al. Ferroptosis: a mixed blessing for infectious diseases. Front Pharmacol, 2022, 13: 992734.
26.	Amaral EP, Namasivayam S, Costa DL, et al. The transcription factor BACH1 promotes tissue damage and host susceptibility in Mycobacterium tuberculosis infection by reducing expression of Gpx4, a major negative regulator of ferroptosis. J Immunol, 2020, 204(Suppl 1): 227.16.
27.	Amaral EP, Namasivayam S, Queiroz ATL, et al. BACH1 promotes tissue necrosis and Mycobacterium tuberculosis susceptibility. Nat Microbiol, 2024, 9(1): 120-135.
28.	Aberman K, Fisher L, Oland S, et al. The transcription factor Bach1 plays an important role in regulating macrophage ferroptosis upon iron supplementation. J Immunol, 2021, 206(Suppl 1): 111.15.
29.	Wufuer D, Li Y, Aierken H, et al. Bioinformatics-led discovery of ferroptosis-associated diagnostic biomarkers and molecule subtypes for tuberculosis patients. Eur J Med Res, 2023, 28(1): 445.
30.	Chen L, Hua J, Dai X, et al. Assessment of ferroptosis-associated gene signatures as potential biomarkers for differentiating latent from active tuberculosis in children. Microb Genom, 2023, 9(5): mgen000997.
31.	Liang T, Chen J, Xu G, et al. Ferroptosis-related gene SOCS1, a marker for tuberculosis diagnosis and treatment, involves in macrophage polarization and facilitates bone destruction in tuberculosis. Tuberculosis (Edinb), 2022, 132: 102140.
32.	叶江娥, 方雪晖, 熊延军, 等. 基于转录组学和机器学习算法的肺结核铁死亡相关关键基因的研究. 中国防痨杂志, 2024, 46(1): 92-99.
33.	Minchella PA, Donkor S, McDermid JM, et al. Iron homeostasis and progression to pulmonary tuberculosis disease among household contacts. Tuberculosis (Edinb), 2015, 95(3): 288-293.
34.	McDermid JM, Hennig BJ, van der Sande M, et al. Host iron redistribution as a risk factor for incident tuberculosis in HIV infection: an 11-year retrospective cohort study. BMC Infect Dis, 2013, 13: 48.
35.	Dai Y, Shan W, Yang Q, et al. Biomarkers of iron metabolism facilitate clinical diagnosis in Mycobacterium tuberculosis infection. Thorax, 2019, 74(12): 1161-1167.

1. World Health Organization. WHO TB knowledge sharing platform. Geneva: World Health Organization, 2023.
2. Jiang X, Stockwell BR, Conrad M. Ferroptosis: mechanisms, biology and role in disease. Nat Rev Mol Cell Biol, 2021, 22(4): 266-282.
3. Chen X, Li J, Kang R, et al. Ferroptosis: machinery and regulation. Autophagy, 2021, 17(9): 2054-2081.
4. Amaral EP, Costa DL, Namasivayam S, et al. A major role for ferroptosis in Mycobacterium tuberculosis-induced cell death and tissue necrosis. J Exp Med, 2019, 216(3): 556-570.
5. Yan R, Xie E, Li Y, et al. The structure of erastin-bound xCT-4F2hc complex reveals molecular mechanisms underlying erastin-induced ferroptosis. Cell Res, 2022, 32(7): 687-690.
6. Chen H, Qi Q, Wu N, et al. Aspirin promotes RSL3-induced ferroptosis by suppressing mTOR/SREBP-1/SCD1-mediated lipogenesis in PIK3CA-mutant colorectal cancer. Redox Biol, 2022, 55: 102426.
7. Dixon SJ, Lemberg KM, Lamprecht MR, et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell, 2012, 149(5): 1060-1072.
8. Lin Z, Liu J, Long F, et al. The lipid flippase SLC47A1 blocks metabolic vulnerability to ferroptosis. Nat Commun, 2022, 13(1): 7965.
9. Li C, Zhang Y, Liu J, et al. Mitochondrial DNA stress triggers autophagy-dependent ferroptotic death. Autophagy, 2021, 17(4): 948-960.
10. Lee H, Zandkarimi F, Zhang Y, et al. Energy-stress-mediated AMPK activation inhibits ferroptosis. Nat Cell Biol, 2020, 22(2): 225-234.
11. Sang M, Luo R, Bai Y, et al. Mitochondrial membrane anchored photosensitive nano-device for lipid hydroperoxides burst and inducing ferroptosis to surmount therapy-resistant cancer. Theranostics, 2019, 9(21): 6209-6223.
12. Dorman SE, Schumacher SG, Alland D, et al. Xpert MTB/RIF ultra for detection of Mycobacterium tuberculosis and rifampicin resistance: a prospective multicentre diagnostic accuracy study. Lancet Infect Dis, 2018, 18(1): 76-84.
13. Trébucq A, Enarson DA, Chiang CY, et al. Xpert^® MTB/RIF for national tuberculosis programmes in low-income countries: when, where and how?. Int J Tuberc Lung Dis, 2011, 15(12): 1567-1572.
14. Amaral EP, Foreman TW, Namasivayam S, et al. GPX4 regulates cellular necrosis and host resistance in Mycobacterium tuberculosis infection. J Exp Med, 2022, 219(11): e20220504.
15. Qiang L, Zhang Y, Lei Z, et al. A mycobacterial effector promotes ferroptosis-dependent pathogenicity and dissemination. Nat Commun, 2023, 14(1): 1430.
16. Kassovska-Bratinova S, Yang G, Igarashi K, et al. Bach1 modulates heme oxygenase-1 expression in the neonatal mouse lung. Pediatr Res, 2009, 65(2): 145-149.
17. Yamada N, Yamaya M, Okinaga S, et al. Microsatellite polymorphism in the heme oxygenase-1 gene promoter is associated with susceptibility to emphysema. Am J Hum Genet, 2000, 66(1): 187-195.
18. Abdalla MY, Ahmad IM, Switzer B, et al. Induction of heme oxygenase-1 contributes to survival of Mycobacterium abscessus in human macrophages-like THP-1 cells. Redox Biol, 2015, 4: 328-339.
19. Costa DL, Namasivayam S, Amaral EP, et al. Pharmacological inhibition of host heme oxygenase-1 suppresses Mycobacterium tuberculosis infection in vivo by a mechanism dependent on tlymphocytes. mBio, 2016, 7(5): e01675-16.
20. Scharn CR, Collins AC, Nair VR, et al. Heme oxygenase-1 regulates inflammation and mycobacterial survival in human macrophages during Mycobacterium tuberculosis infection. J Immunol, 2016, 196(11): 4641-4649.
21. Andrade BB, Pavan Kumar N, Mayer-Barber KD, et al. Plasma heme oxygenase-1 levels distinguish latent or successfully treated human tuberculosis from active disease. PLoS One, 2013, 8(5): e62618.
22. Andrade BB, Pavan Kumar N, Amaral EP, et al. Heme oxygenase-1 regulation of matrix metalloproteinase-1 expression underlies distinct disease profiles in Tuberculosis. J Immunol, 2015, 195(6): 2763-2773.
23. Reddy VP, Chinta KC, Saini V, et al. Ferritin H deficiency in myeloid compartments dysregulates host energy metabolism and increases susceptibility to Mycobacterium tuberculosis infection. Front Immunol, 2018, 9: 860.
24. Yang S, Ouyang J, Lu Y, et al. A dual role of heme oxygenase-1 in tuberculosis. Front Immunol, 2022, 13: 842858.
25. Xiao L, Huang H, Fan S, et al. Ferroptosis: a mixed blessing for infectious diseases. Front Pharmacol, 2022, 13: 992734.
26. Amaral EP, Namasivayam S, Costa DL, et al. The transcription factor BACH1 promotes tissue damage and host susceptibility in Mycobacterium tuberculosis infection by reducing expression of Gpx4, a major negative regulator of ferroptosis. J Immunol, 2020, 204(Suppl 1): 227.16.
27. Amaral EP, Namasivayam S, Queiroz ATL, et al. BACH1 promotes tissue necrosis and Mycobacterium tuberculosis susceptibility. Nat Microbiol, 2024, 9(1): 120-135.
28. Aberman K, Fisher L, Oland S, et al. The transcription factor Bach1 plays an important role in regulating macrophage ferroptosis upon iron supplementation. J Immunol, 2021, 206(Suppl 1): 111.15.
29. Wufuer D, Li Y, Aierken H, et al. Bioinformatics-led discovery of ferroptosis-associated diagnostic biomarkers and molecule subtypes for tuberculosis patients. Eur J Med Res, 2023, 28(1): 445.
30. Chen L, Hua J, Dai X, et al. Assessment of ferroptosis-associated gene signatures as potential biomarkers for differentiating latent from active tuberculosis in children. Microb Genom, 2023, 9(5): mgen000997.
31. Liang T, Chen J, Xu G, et al. Ferroptosis-related gene SOCS1, a marker for tuberculosis diagnosis and treatment, involves in macrophage polarization and facilitates bone destruction in tuberculosis. Tuberculosis (Edinb), 2022, 132: 102140.
32. 叶江娥, 方雪晖, 熊延军, 等. 基于转录组学和机器学习算法的肺结核铁死亡相关关键基因的研究. 中国防痨杂志, 2024, 46(1): 92-99.
33. Minchella PA, Donkor S, McDermid JM, et al. Iron homeostasis and progression to pulmonary tuberculosis disease among household contacts. Tuberculosis (Edinb), 2015, 95(3): 288-293.
34. McDermid JM, Hennig BJ, van der Sande M, et al. Host iron redistribution as a risk factor for incident tuberculosis in HIV infection: an 11-year retrospective cohort study. BMC Infect Dis, 2013, 13: 48.
35. Dai Y, Shan W, Yang Q, et al. Biomarkers of iron metabolism facilitate clinical diagnosis in Mycobacterium tuberculosis infection. Thorax, 2019, 74(12): 1161-1167.

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Research progress of ferroptosis in pulmonary tuberculosis

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