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EgCF mediates macrophage polarisation by influencing the glycolytic pathway

Published online by Cambridge University Press:  21 December 2023

Yeye Feng
Affiliation:
NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, the First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang, China Department of Immunology, Shihezi University School of Medicine, Shihezi, Xinjiang, China
Junying Xu
Affiliation:
NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, the First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang, China Department of Immunology, Shihezi University School of Medicine, Shihezi, Xinjiang, China
Junxia Lu
Affiliation:
NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, the First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang, China Department of Immunology, Shihezi University School of Medicine, Shihezi, Xinjiang, China
Jun Hou
Affiliation:
NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, the First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang, China Department of Immunology, Shihezi University School of Medicine, Shihezi, Xinjiang, China
Lianghai Wang
Affiliation:
NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, the First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang, China
Dan Dong
Affiliation:
NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, the First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang, China Department of Immunology, Shihezi University School of Medicine, Shihezi, Xinjiang, China
Xian Wang
Affiliation:
NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, the First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang, China Department of Immunology, Shihezi University School of Medicine, Shihezi, Xinjiang, China
Xiaofang Wang
Affiliation:
NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, the First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang, China Department of Immunology, Shihezi University School of Medicine, Shihezi, Xinjiang, China
Xiangwei Wu*
Affiliation:
NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, the First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang, China Department of General Surgery, the First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang, China
Xueling Chen*
Affiliation:
NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, the First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang, China Department of Immunology, Shihezi University School of Medicine, Shihezi, Xinjiang, China
*
Corresponding authors: Xueling Chen and Xiangwei Wu; Emails: chenxueling@shzu.edu.cn; wxwshz@126.com
Corresponding authors: Xueling Chen and Xiangwei Wu; Emails: chenxueling@shzu.edu.cn; wxwshz@126.com

Abstract

Human cystic echinococcosis (CE) is a zoonotic disorder triggered by the larval stage of Echinococcus granulosus (E. granulosus) and predominantly occurred in the liver and lungs. The M2 macrophage level is considerably elevated among the liver of patients with hepatic CE and performs an integral function in liver fibrosis. However, the mechanism of CE inducing polarisation of macrophage to an M2 phenotype is unknown. In this study, macrophage was treated with E. granulosus cyst fluid (EgCF) to explore the mechanism of macrophage polarisation. Consequently, the expression of the M2 macrophage and production of anti-inflammatory cytokines increased after 48 h treatment by EgCF. In addition, EgCF promoted polarisation of macrophage to an M2 phenotype by inhibiting the expression of transcriptional factor hypoxia-inducible factor 1-alpha (HIF-1α), which increased the expression of glycolysis-associated genes, including hexokinase 2 (HK2) and pyruvate kinase 2 (PKM2). The HIF-1α agonist ML228 also inhibited the induction of macrophage to an M2 phenotype by EgCF in vitro. Our findings indicate that E. granulosus inhibits glycolysis by suppressing the expression of HIF-1α.

Type
Research Paper
Copyright
© The Author(s), 2023. Published by Cambridge University Press

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Footnotes

*

Authors with equal contribution.

References

Ahmed, F, Ibrahim, A, Cooper, CL, Kumar, A and Crawley, AM (2019). Chronic hepatitis C virus infection impairs M1 macrophage differentiation and contributes to CD8(+) T-cell dysfunction. Cells 8(4). doi: 10.3390/cells8040374.Google Scholar
Agudelo Higuita, NI, Brunetti, E and McCloskey, C (2016). Cystic Echinococcosis. J Clin Microbiol 54(3), 518523. doi: 10.1128/jcm.02420-15.Google Scholar
Ambade, A, Satishchandran, A, Saha, B, Gyongyosi, B, Lowe, P, Kodys, K, Catalano, D, Szabo, G (2016) Hepatocellular carcinoma is accelerated by NASH involving M2 macrophage polarization mediated by hif-1αinduced IL-10. Oncoimmunology 5(10), e1221557. doi: 10.1080/2162402x.2016.1221557.Google Scholar
Budke, CM, Carabin, H, Ndimubanzi, PC, Nguyen, H, Rainwater, E, Dickey, M, Bhattarai, R, Zeziulin, O, Qian, MB (2013) A systematic review of the literature on cystic echinococcosis frequency worldwide and its associated clinical manifestations. Am J Trop Med Hyg 88(6), 10111027. doi: 10.4269/ajtmh.12-0692.Google Scholar
Chen, C, Dong, D, Fan, H, Jiang, H, Hou, J, Yang, K, Guo, F, Chen, X (2017) ProCEs in vitro stimulate macrophages to highly express PPAR α/γ and regulate their polarization. Chinese Journal of Immunology (in Chinese) 33(01), 1619+24. doi: 10.3969/j.issn.Google Scholar
Cheng, Y, Feng, Y, Xia, Z, Li, X and Rong, J (2017) ω-Alkynyl arachidonic acid promotes anti-inflammatory macrophage M2 polarization against acute myocardial infarction via regulating the cross-talk between PKM2, HIF-1α and iNOS. Biochim. Biophys Acta Mol Cell Biol Lipids 1862(12), 15951605. doi: 10.1016/j.bbalip.2017.09.009.Google Scholar
Chen, X, Fu, E, Lou, H, Mao, X, Yan, B, Tong, F, Sun, J, Wei, L (2019) IL-6 induced M1 type macrophage polarization increases radiosensitivity in HPV positive head and neck cancer. Cancer Lett 456, 6979. doi: 10.1016/j.canlet.2019.04.032.Google Scholar
Dabral, S, Muecke, C, Valasarajan, C, Schmoranzer, M, Wietelmann, A, Semenza, GL, Meister, M, Muley, T, Seeger-Nukpezah, T, Samakovlis, C, Weissmann, N, Grimminger, F, Seeger, W, Savai, R, Pullamsetti, SS (2019) A RASSF1A-HIF1α loop drives Warburg effect in cancer and pulmonary hypertension. Nat Commun 10(1), 2130. doi: 10.1038/s41467-019-10044-z.Google Scholar
Deplazes, P, Rinaldi, L, Alvarez Rojas, CA, Torgerson, PR, Harandi, MF, Romig, T, Antolova, D, Schurer, JM, Lahmar, S, Cringoli, G, Magambo, J, Thompson, RC, Jenkins, EJ (2017) Global distribution of alveolar and cystic echinococcosis. Adv Parasitol 95, 315493. doi: 10.1016/bs.apar.2016.11.001.Google Scholar
Duan, M, Yang, Y, Peng, S, Liu, X, Zhong, J, Guo, Y, Lu, M, Nie, H, Ren, B, Zhang, X, Liu, L (2019) C/EBP homologous protein (CHOP) activates macrophages and promotes liver fibrosis in Schistosoma japonicum-infected mice. J Immunol Res 2019, 5148575. doi: 10.1155/2019/5148575.Google Scholar
Fan, J, Shan, C, Kang, HB, Elf, S, Xie, J, Tucker, M, Gu, TL, Aguiar, M, Lonning, S, Chen, H, Mohammadi, M, Britton, LM, Garcia, BA, Alečković, M, Kang, Y, Kaluz, S, Devi, N, Van Meir, EG, Hitosugi, T, Seo, JH, Lonial, S, Gaddh, M, Arellano, M, Khoury, HJ, Khuri, FR, Boggon, TJ, Kang, S, Chen, J (2014) Tyr phosphorylation of PDP1 toggles recruitment between ACAT1 and SIRT3 to regulate the pyruvate dehydrogenase complex. Mol Cell 53(4), 534548. doi: 10.1016/j.molcel.2013.12.026.CrossRefGoogle ScholarPubMed
Gottstein, B, Soboslay, P, Ortona, E, Wang, J, Siracusano, A and Vuitton, D (2017) Immunology of alveolar and cystic echinococcosis (AE and CE). Adv Parasitol 96, 154. doi: 10.1016/bs.apar.2016.09.005.Google Scholar
Jafari, R, Sanei, B, Baradaran, A, Kolahdouzan, M, Bagherpour, B and Yousofi Darani, H (2019) Immunohistochemical observation of local inflammatory cell infiltration in the host-tissue reaction site of human hydatid cysts. J Helminthol 93(3), 277285. doi: 10.1017/s0022149x1800024x.Google Scholar
Jiang, X, Zhang, X, Jiang, N, Sun, Y, Li, T, Zhang, J, Shen, Y, Cao, J (2022) The single-cell landscape of cystic echinococcosis in different stages provided insights into endothelial and immune cell heterogeneity. Front Immunol 13, 1067338. doi: 10.3389/fimmu.2022.1067338.CrossRefGoogle ScholarPubMed
Kern, P, Menezes da Silva, A, Akhan, O, Müllhaupt, B, Vizcaychipi, KA, Budke, C and Vuitton, DA (2017) The echinococcoses: Diagnosis, clinical management and burden of disease. Adv Parasitol 96, 259369. doi: 10.1016/bs.apar.2016.09.006.Google Scholar
Kimura, T, Nada, S, Takegahara, N, Okuno, T, Nojima, S, Kang, S, Ito, D, Morimoto, K, Hosokawa, T, Hayama, Y, Mitsui, Y, Sakurai, N, Sarashina-Kida, H, Nishide, M, Maeda, Y, Takamatsu, H, Okuzaki, D, Yamada, M, Okada, M, Kumanogoh, A (2016) Polarization of M2 macrophages requires Lamtor1 that integrates cytokine and amino-acid signals. Nat Commun 7, 13130. doi: 10.1038/ncomms13130.Google Scholar
Kumar, P, Misra, P, Thakur, CP, Saurabh, A, Rishi, N and Mitra, DK (2018) T cell suppression in the bone marrow of visceral leishmaniasis patients: Impact of parasite load. Clin Exp Immunol 191(3), 318327. doi: 10.1111/cei.13074.Google Scholar
Li, B, Liu, YM, Yan, Y, Yang, N, Gao, J, Jiang, T, Shang, XQ, Tian, FM, Ding, JB, Ma, XM (2019) Effect of different types of macrophages on hepatic fibrosis in Echinococcus granulosus mice. Biomed Pharmacother 117, 109178. doi: 10.1016/j.biopha.2019.109178.Google Scholar
Li, YQ, Chen, YF, Dang, YP, Wang, Y, Shang, ZZ, Ma, Q, Wang, YJ, Zhang, J, Luo, L, Li, QQ, Zhao, L (2017) Corilagin counteracts IL-13Rα1 signaling pathway in macrophages to mitigate schistosome egg-induced hepatic fibrosis. Front Cell Infect Microbiol 7, 443. doi: 10.3389/fcimb.2017.00443.Google Scholar
Mills, EL, Kelly, B, Logan, A, Costa, ASH, Varma, Bryant CE Tourlomousis, P, Däbritz, JHM, Gottlieb, E, Latorre, I, Corr, SC, McManus, G, Ryan, D, Jacobs, HT, Szibor, M, Xavier, RJ, Braun, T, Frezza, C, Murphy, MP, O’Neill, LA (2016) Succinate dehydrogenase supports metabolic repurposing of mitochondria to drive inflammatory macrophages. Cell 167(2), 457470.e413. doi: 10.1016/j.cell.2016.08.064.CrossRefGoogle ScholarPubMed
Nonnenmacher, Y and Hiller, K (2018) Biochemistry of proinflammatory macrophage activation. Cell Mol Life Sci 75(12), 20932109. doi: 10.1007/s00018-018-2784-1.Google Scholar
Palazon, A, Goldrath, AW, Nizet, V and Johnson, RS (2014) HIF transcription factors, inflammation, and immunity. Immunity 41(4), 518528. doi: 10.1016/j.immuni.2014.09.008.Google Scholar
Rodriguez, AE, Ducker, GS, Billingham, LK, Martinez, CA, Mainolfi, N, Suri, V, Friedman, A, Manfredi, MG, Weinberg, SE, Rabinowitz, JD, Chandel, NS (2019) Serine metabolism supports macrophage IL-1β production. Cell Metab 29(4), 10031011.e1004. doi: 10.1016/j.cmet.2019.01.014.Google Scholar
Sagasti, C, Casaravilla, C, Fernández, C, Fló, M and Díaz, Á (2021) Inhibition of inflammatory cytokine production and proliferation in macrophages by Kunitz-type inhibitors from Echinococcus granulosus. Mol Biochem Parasitol 242, 111351. doi: 10.1016/j.molbiopara.2021.111351.Google Scholar
Sakamoto, S, Kagawa, S, Kuwada, K, Ito, A, Kajioka, H, Kakiuchi, Y, Watanabe, M, Kagawa, T, Yoshida, R, Kikuchi, S, Kuroda, S, Tazawa, H, Fujiwara, T (2019) Intraperitoneal cancer-immune microenvironment promotes peritoneal dissemination of gastric cancer. Oncoimmunology 8(12), e1671760. doi: 10.1080/2162402X.2019.1671760.Google Scholar
Santos, SAD and Andrade, DRJ (2017) HIF-1alpha and infectious diseases: A new frontier for the development of new therapies. Rev Inst Med Trop Sao Paulo 59, e92. doi: 10.1590/s1678-9946201759092.CrossRefGoogle ScholarPubMed
Shapouri-Moghaddam, A, Mohammadian, S, Vazini, H, Taghadosi, M, Esmaeili, SA, Mardani, F, Seifi, B, Mohammadi, A, Afshari, JT, Sahebkar, A (2018) Macrophage plasticity, polarization, and function in health and disease. J Cell Physiol 233(9), 64256440. doi: 10.1002/jcp.26429.Google Scholar
Silva-Álvarez, V, Folle, AM, Ramos, AL, Kitano, ES, Iwai, LK, Corraliza, I, Córsico, B, Ferreira, AM (2016) Echinococcus granulosus Antigen B binds to monocytes and macrophages modulating cell response to inflammation. Parasit Vectors 9, 69. doi: 10.1186/s13071-016-1350-7.Google Scholar
Siracusano, A, Margutti, P, Delunardo, F, Profumo, E, Riganò, R, Buttari, B, … Ortona, E (2008) Molecular cross-talk in host-parasite relationships: The intriguing immunomodulatory role of Echinococcus antigen B in cystic echinococcosis. Int J Parasitol 38(12), 13711376. doi: 10.1016/j.ijpara.2008.06.003.Google Scholar
Spence, S, Fitzsimons, A, Boyd, CR, Kessler, J, Fitzgerald, D, Elliott, J, Gabhann, JN, Smith, S, Sica, A, Hams, E, Saunders, SP, Jefferies, CA, Fallon, PG, McAuley, DF, Kissenpfennig, A, Johnston, JA (2013) Suppressors of cytokine signaling 2 and 3 diametrically control macrophage polarization. Immunity 38(1), 6678. doi: 10.1016/j.immuni.2012.09.013.Google Scholar
Torgerson, PR, Devleesschauwer, B, Praet, N, Speybroeck, N, Willingham, AL, Kasuga, F, Rokni, MB, Zhou, XN, Fèvre, EM, Sripa, B, Gargouri, N, Fürst, T, Budke, CM, Carabin, H, Kirk, MD, Angulo, FJ, Havelaar, A, de Silva, N (2015) World Health Organization estimates of the global and regional disease burden of 11 foodborne parasitic diseases, 2010: A data synthesis. PLoS Med 12(12), e1001920. doi: 10.1371/journal.pmed.1001920.Google Scholar
Velasco-Tirado, V, Alonso-Sardón, M, Lopez-Bernus, A, Romero-Alegría, Á, Burguillo, FJ, Muro, A, Carpio-Pérez, A, Muñoz Bellido, JL, Pardo-Lledias, J, Cordero, M, Belhassen-García, M (2018). Medical treatment of cystic echinococcosis: Systematic review and meta-analysis. BMC Infect Dis 18(1), 306. doi: 10.1186/s12879-018-3201-y.Google Scholar
Vuitto, DA (2003) The ambiguous role of immunity in echinococcosis: Protection of the host or of the parasite? Acta Trop 85(2), 119132. doi: 10.1016/s0001-706x(02)00230-9.CrossRefGoogle Scholar
Vukman, KV, Adams, PN, Metz, M, Maurer, M and O’Neill, SM (2013) Fasciola hepatica tegumental coat impairs mast cells’ ability to drive Th1 immune responses. J Immunol 190(6), 28732879. doi: 10.4049/jimmunol.1203011.Google Scholar
Wang, E, Liao, Z, Wang, L, Liao, Y, Xu, X, Liu, P, Wang, X, Hou, J, Jiang, H, Wu, X, Chen, X (2021) A combination of pirfenidone and TGF-β inhibition mitigates cystic echinococcosis-associated hepatic injury. Parasitology 148(7), 767778. doi: 10.1017/s0031182021000287.Google Scholar
Wang, X, Du, H and Li, X. (2021) Artesunate attenuates atherosclerosis by inhibiting macrophage M1-like polarization and improving metabolism. International Immunopharmacology 102, 108413. doi: 10.1016/j.intimp.2021.108413.Google Scholar
Wang, YC, Wu, YS, Hung, CY, Wang, SA, Young, MJ, Hsu, TI and Hung, JJ (2018) USP24 induces IL-6 in tumor-associated microenvironment by stabilizing p300 and β-TrCP and promotes cancer malignancy. Nat Commun 9(1), 3996. doi: 10.1038/s41467-018-06178-1.Google Scholar
Wen, H, Vuitton, L, Tuxun, T, Li, J, Vuitton, D.A, Zhang, W and McManus, DP (2019) Echinococcosis: Advances in the 21st century. Clin Microbiol Rev 32(2). doi: 10.1128/cmr.00075-18.Google Scholar
Werno, C, Menrad, H, Weigert, A, Dehne, N, Goerdt, S, Schledzewski, K, Kzhyshkowska, J, Brüne, B (2010) Knockout of HIF-1α in tumor-associated macrophages enhances M2 polarization and attenuates their pro-angiogenic responses. Carcinogenesis 31(10), 18631872. doi: 10.1093/carcin/bgq088.CrossRefGoogle ScholarPubMed
Xu, L, Huan, L, Guo, T, Wu, Y, Liu, Y, Wang, Q, Huang, S, Xu, Y, Liang, L, He, X (2020) LncRNA SNHG11 facilitates tumor metastasis by interacting with and stabilizing HIF-1α. Oncogene 39(46), 70057018. doi: 10.1038/s41388-020-01512-8.Google Scholar
Yasen, A, Li, W, Ran, B, Aini, A, Wang, Z, Jiang, T, Shao, Y, Aji, T, Wen, H (2021) Identification of infiltrating immune cell subsets and heterogeneous macrophages in the lesion microenvironment of hepatic cystic echinococcosis patients with different cyst viability. Acta Trop 221, 106029. doi: 10.1016/j.actatropica.2021.106029.Google Scholar
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