Role of macrophage extracellular traps in infectious diseases

doi:10.16352/j.issn.1001-6325.2026.03.0450

Abstract

Abstract: Macrophage extracellular traps (METs) are newly discovered mechanism of immune system. Like neutrophil extracellular traps (NETs), their role in infectious diseases has not been fully elucidated. METs participate in host defense by releasing components such as DNA, histones, and antimicrobial proteins; However, their excessive or abnormal activation may exacerbate inflammatory responses and cause tissue damage. This article reviews the biological characteristics of METs, their activation pathways, and their potential mechanism of action in infectious diseases of various systems. It also explores METs- targeted therapeutic strategies, such as inhibiting METs formation or promoting their clearance to alleviate inflammatory responses, aiming to provide new theoretical basis and potential therapeutic targets for the treatment of infectious diseases.

Key words: macrophage extracellular traps(METs), infectious disease, immune defense, therapeutic strategies

CLC Number:

R364.7

YUAN Jiamin, FANG Chengchao, JIANG Junsheng. Role of macrophage extracellular traps in infectious diseases[J]. Basic & Clinical Medicine, 2026, 46(3): 450-455.

References

[1] Brinkmann V, Reichard U, Goosmann C, et al. Neutrophil extracellular traps kill bacteria[J].Science,2004,303:1532-1535.doi:10.1126/science.1092385.
[2] Conceição-Silva F, Reis CSM, De Luca PM, et al. The immune system throws its traps: cells and their extracellular traps in disease and protection[J].Cells, 2021,10:1891. doi:10.3390/cells10081891.
[3] Park MD, Silvin A, Ginhoux F, et al. Macrophages in health and disease[J].Cell, 2022,185:4259-4279. doi:10.1016/j.cell.2022.10.007.
[4] Chow OA, von Köckritz-Blickwede M, Bright AT, et al. Statins enhance formation of phagocyte extracellular traps[J].Cell Host Microbe, 2010,8:445-454.
[5] Wei Z, Guo X, Wang J, et al. T-2 toxin triggers immune toxicity by enhancing glycolysis and activating TLR2/4-MAPK signaling pathways in bovine[J].Toxicol Appl Pharmacol, 2025,503:117485. doi:10.1016/j.taap.2025.117485.
[6] Baz AA, Chen S, Hao H, et al. Macrophage extracellular traps are induced by Mycoplasma bovis in bovine macrophages through NADPH oxidase/ROS-dependent manner and their antibacterial efficacy[J].FASEB J, 2024,38:e70238. doi:10.1096/fj.202402304R.
[7] Zhai QA, Zhang XC, Zhang HB, et al. Pentatrichomonas hominis induces extracellular traps formation of macrophages via the TLR2/NADPH/PAD4 pathway[J].Parasit Vectors, 2025,18:248. doi:10.1186/s13071-025-06840-w.
[8] Liu ZZ, Chen W, Zhou CK, et al. Stimulator of interferon genes (STING) promotes Staphylococcus aureus-induced extracellular traps formation via the ROS-ERK signaling pathway[J].Front Cell Dev Biol, 2022,10:836880. doi:10.3389/fcell.2022.836880.
[9] López-Acosta O, Ruiz-Ramírez A, Barrios-Maya MÁ, et al. Lipotoxicity, glucotoxicity and some strategies to protect vascular smooth muscle cell against proliferative phenotype in metabolic syndrome[J].Food Chem Toxicol, 2023,172:113546.doi:10.1016/j.fct.2022.113546.
[10] Mishra N, Mohs M, Wittmann N, et al. PLC and PAD2 regulate extracellular calcium-triggered release of macrophage extracellular DNA traps[J].Eur J Immunol, 2025,55:e202350942. doi:10.1002/eji.202350942.
[11] Bashar SJ, Holmes CL, Shelef MA. Macrophage extracellular traps require peptidylarginine deiminase 2 and 4 and are a source of citrullinated antigens bound by rheumatoid arthritis autoantibodies[J].Front Immunol, 2024,15:1167362.doi:10.3389/fimmu.2024.1167362.
[12] Wu Z, Tian Y, Alam HB, et al. Peptidylarginine deiminases 2 mediates caspase-1-associated lethality in Pseudomonas aeruginosa pneumonia-induced sepsis[J].J Infect Dis, 2022,223:1093-1102.doi:10.1093/infdis/jiaa475.
[13] Yu X, Song Y, Dong T, et al. Citrullination of NF-κB p65 by PAD2 as a novel therapeutic target for modulating macrophage polarization in acute lung injury[J].Adv Sci (Weinh), 2025,12:e2413253.doi:10.1002/advs.202413253.
[14] Zhao X, Tang X, Guo N, et al. Biochanin a enhances the defense against Salmonella enterica infection through AMPK/ULK1/mTOR-mediated autophagy and extracel-lular traps and reversing SPI-1-dependent macrophage (MΦ) M2 polarization[J].Front Cell Infect Microbiol, 2018,8:318. doi:10.3389/fcimb.2018.00318.
[15] Webster SJ, Daigneault M, Bewley MA, et al. Distinct cell death programs in monocytes regulate innate responses following challenge with common causes of invasive bacterial disease[J].J Immunol, 2010,185:2968-2979. doi:10.4049/jimmunol.1000805.
[16] García-Bengoa M, Meurer M, Goethe R, et al.Role of phagocyte extracellular traps during Mycobacterium tuberculosis infections and tuberculosis disease processes[J].Front Microbiol, 2023,14:983299. doi:10.3389/fmicb.2023.983299.
[17] 吴倩倩,马楷婷,曹凌飞,等.巨噬细胞胞外诱捕网在炎性疾病中的作用[J].基础医学与临床,2025,45:1368-1371.doi:10.16352/j.issn.1001-6325.2025.10.1368.
[18] Periselneris J, Turner CT, Ercoli G, et al. Pneumolysin suppresses the initial macrophage pro-inflammatory response to Streptococcus pneumoniae[J].Immunology,2022,167:413-427.doi:10.1111/imm.13546.
[19] Papanicolaou A, Wang H, McQualter J, et al. House dust mite aeroallergen suppresses leukocyte phagocytosis and netosis initiated by pneumococcal lung infection[J].Front Pharmacol, 2022,13:835848. doi:10.3389/fphar.2022.835848.
[20] Kang H, Liu T, Wang Y, et al. Neutrophil-macrophage communication via extracellular vesicle transfer promotes itaconate accumulation and ameliorates cytokine storm syndrome[J].Cell Mol Immunol, 2024,21:689-706. doi:10.1038/s41423-024-01174-6.
[21] Doster RS, Sutton JA, Rogers LM, et al. Streptococcus agalactiae induces placental macrophages to release extracellular traps loaded with tissue remodeling enzymes via an oxidative burst-dependent mechanism[J].mBio, 2018,9:e02084-18. doi:10.1128/mBio.02084-18.
[22] Yue L, Yan M, Chen S, et al. PTP1B negatively regulates STAT1-independent Pseudomonas aeruginosa killing by macrophages[J].Biochem Biophys Res Commun,2020,533:296-303. doi:10.1016/j.bbrc.2020.09.032.
[23] Skopelja-Gardner S, Theprungsirikul J, Lewis KA, et al. Regulation of Pseudomonas aeruginosa-mediated neutrophil extracellular traps[J].Front Immunol, 2019,10:1670. doi:10.3389/fimmu.2019.01670.
[24] Zhou L, Li Y, You J, et al. Salmonella spvC gene suppresses macrophage/neutrophil antibacterial defense mediated by gasdermin D[J].Inflamm Res, 2024,73:19-33. doi:10.1007/s00011-023-01818-9.
[25] Li L, Jiao Q, Yang Q, et al. A bladder-blood immune barrier constituted by suburothelial perivascular macrophages restrains uropathogen dissemination[J].Immunity,2025,58:568-584.e6.doi:10.1016/j.immuni.2025.02.002.
[26] Baz AA, Hao H, Lan S, et al. Emerging insights into macrophage extracellular traps in bacterial infections[J].FASEB J, 2024,38:e23767. doi:10.1096/fj.202400739R.
[27] Doster RS, Sutton JA, Rogers LM, et al.Streptococcus agalactiae induces placental macrophages to release extracellular traps loaded with tissue remodeling enzymes via an oxidative burst-dependent mechanism[J].mBio, 2018,9:e02084-18.doi:10.1128/mBio.02084-18.
[28] 黄赛赛,孙玥,陈子嫣,等.巨噬细胞胞外诱捕网在类风湿关节炎患者滑膜中的表达及其临床意义[J].临床检验杂志,2022,40:330-335.
[29] Shen Y, Shi R, Lu S, et al. Role of peptidyl arginine deiminase 4-dependent macrophage extracellular trap formation in type 1 diabetes pathogenesis[J].Diabetes, 2024,73:1862-1874. doi:10.2337/db23-1000.