Parasites, Hosts and Diseases

The Korea Society for Parasitology and Tropical Medicine (대한기생충학·열대의학회)
권호 표지
DOI QR코드

DOI QR Code

Suppressed Production of Pro-inflammatory Cytokines by LPS-Activated Macrophages after Treatment with Toxoplasma gondii Lysate

  • Lee, Eun-Jung (Department of Parasitology and Institute of Biomedical Science, Hanyang University College of Medicine) ;
  • Heo, Yoo-Mi (Department of Parasitology and Institute of Biomedical Science, Hanyang University College of Medicine) ;
  • Choi, Jong-Hak (Department of Parasitology and Institute of Biomedical Science, Hanyang University College of Medicine) ;
  • Song, Hyun-Ouk (Department of Parasitology and Institute of Biomedical Science, Hanyang University College of Medicine) ;
  • Ryu, Jae-Sook (Department of Parasitology and Institute of Biomedical Science, Hanyang University College of Medicine) ;
  • Ahn, Myoung-Hee (Department of Parasitology and Institute of Biomedical Science, Hanyang University College of Medicine)
  • Published : 2008.09.30
Download PDF
⟨ Previous Next ⟩

Abstract

During Toxoplasma gondii infection, macrophages, dendritic cells, and neutrophils are important sources of pro-inflammatory cytokines from the host. To counteract the pro-inflammatory activities, T. gondii is known to have several mechanisms inducing down-regulation of the host immunity. In the present study, we analyzed the production of pro- and anti-inflammatory cytokines from a human myelomonocytic cell line, THP-1 cells, in response to treatment with T. gondii lysate or lipopolysaccharide (LPS). Treatment of THP-1 cells with LPS induced production of IL-12, TNF-$\alpha$, IL-8, and IL-10. Co-treatment of THP-1 cells with T. gondii lysate inhibited the LPS-induced IL-12, IL-8 and TNF-$\alpha$ expression, but increased the level of IL-10 synergistically. IL-12 and IL-10 production was down-regulated by anti-human toll-like receptor (TLR)-2 and TLR4 antibodies. T. gondii lysate triggered nuclear factor (NF)-${\kappa}B$-dependent IL-8 expression in HEK293 cells transfected with TLR2. It is suggested that immunosuppression induced by T. gondii lysate treatment might occur via TLR2-mediated NF-${\kappa}B$ activation.

Keywords

References

  1. Langermans JA, Nibbering PH, Van Vuren-Van Der Halst ME, Van Furth R. Transforming growth factor-beta suppresses interferon- gamma-induced toxoplasmastatic activity in murine macrophages by inhibition of tumor necrosis factor- alpha production. Parasite Immunol 2001; 23: 169-175 https://doi.org/10.1046/j.1365-3024.2001.00371.x
  2. Lin W, Karin M. A cytokine-mediated link between innate immunity, inflammation, and cancer. J Clin Invest 2007; 117: 1175-1183 https://doi.org/10.1172/JCI31537
  3. Butcher BA, Kim L, Panopoulos AD, Watowich SS, Murray PJ, Denkers EY. Cutting edge: IL-10-independent STAT3 activation by Toxoplasma gondii mediates suppression of IL-12 and TNF-$\alpha$ in host macrophages. J Immunol 2005; 174: 3148-3152 https://doi.org/10.4049/jimmunol.174.6.3148
  4. Buzoni-Gatel D, Werts C. Toxoplasma gondii and subversion of the immune system. Trends Parasitol 2006; 22: 448-452 https://doi.org/10.1016/j.pt.2006.08.002
  5. Lee CW, Bennouna S, Denkers EY. Screening for Toxoplasma gondii-regulated transcriptional responses in lipopolysaccharideactivated macrophages. Infect Immun 2006; 74: 1916-1923 https://doi.org/10.1128/IAI.74.3.1916-1923.2006
  6. Belloni A, Villenu I, Gomez JE, Polloux H, Bonhomme A, Guenounoh M, Pinon JM, Aubert D. Regulation of tumor necrosis factor alpha and its specific receptors during Toxoplasma gondii infection in human monocytic cells. Parasitol Res 2003; 89: 207- 213
  7. Friedland JS, Shattock RJ, Johnson JD, Remick DG, Holliman RE, Griffin GE. Differential cytokine gene expression and secretion after phagocytosis by a human monocytic cell line of Toxoplasma gondii compared with Mycobacterium tuberculosis. 1993; 91: 282- 286
  8. Butcher BA, Kim L, Johnson PF, Denkers EY. Toxoplasma gondii tachyzoites inhibit proinflammatory cytokine induction in infected macrophages by preventing nuclear translocation of the transcription factor NF-$\kappa$B. J Immunol 2001; 167: 2193-2201 https://doi.org/10.4049/jimmunol.167.4.2193
  9. Lang C, Gross U, Luder CG. Subversion of innate and adaptive immune responses by Toxoplasma gondii. Parasitol Res 2007; 100: 191-203 https://doi.org/10.1007/s00436-006-0306-9
  10. Aldebert D, Durand F, Mercier C, Brenier-Pinchart M, Cesbron- Delauw M, Pellowx H. Toxoplasma gondii triggers secretion of interleukin- 12 but low level of interleukin-10 from the THP-1 human monocyte cell line. Cytokine 2007; 206-211
  11. Zanin-Zhorov A, Tal-Lapidot G, Cahalon L, Cohen-Sfady M, Pevsner- Fischer M, Lider O, Cohen IR. Cutting edge: T cells respond to lipopolysaccharide innately via TLR4 signaling. J Immunol 2007; 179: 41-44 https://doi.org/10.4049/jimmunol.179.1.41
  12. Manson N, Aliberti J, Caamano JC, Liou H, Hunter CA. Identification of c-Rel-dependent and -independent pathways of IL-12 production during infections and inflammatory stimuli. J Immunol 2002; 168: 2590-2594 https://doi.org/10.4049/jimmunol.168.6.2590
  13. Deckert-Schluter M, Buck C, Weiner D, Kaefer N, Rang A, Hof H, Wiestler OD, Schluter D. Interleukin-10 down regulates the intracerebral immune response in chronic Toxoplasma encephalitis. J Neuroimmunol 1997; 76: 167-176 https://doi.org/10.1016/S0165-5728(97)00047-7
  14. Belloni A, Aubert D, Gomez-Marin JE, Naour RL, Bonhomme A, Guenounou M, Pinon JM. Involvement of tumor necrosis factorduring infection of human monocytic cells by Toxoplasma gondii. Parasitol Res 2000; 86: 406-412 https://doi.org/10.1007/s004360050685
  15. Buzoni-Gatel D, Werts C. Toxoplasma gondii and subversion of the immune system. Trends Parasitol 2006; 22: 448-452 https://doi.org/10.1016/j.pt.2006.08.002
  16. Zimmermann S, Murray PJ, Heeg K, Dalpke AH. Induction of suppressor of cytokine signaling-1 by Toxoplasma gondii contributes to immune evasion in macrophages by blocking IFNsignaling. J Immunol 2006; 176: 1840-1847 https://doi.org/10.4049/jimmunol.176.3.1840
  17. Kim JM, Oh YK, Kim YJ, Cho SJ, Ahn MH, Cho YJ. Nuclear factor- kappa B plays a major role in the regulation of chemokine expression of HeLa cells in response to Toxoplasma gondii infection. Parasitol Res 2001; 87: 758-763 https://doi.org/10.1007/s004360100447
  18. Ryu JS, Kang JH, Jung SY, Shin MH, Kim JM, Park H, Min DY. Production of Interleukin-8 by human neutrophils stimulated with Trichomonas vaginalis. Infect Immun 2004; 72: 1326-1332 https://doi.org/10.1128/IAI.72.3.1326-1332.2004
  19. Akira S, Sato S. Toll-like receptors and their signaling mechanisms. Scand J Infect Dis 2003; 35: 555-562 https://doi.org/10.1080/00365540310015683
  20. Urematsu S, Akira S. Toll-like receptor and innate immunity. J Mol Med 2006; 84: 712-725 https://doi.org/10.1007/s00109-006-0084-y
  21. Tapping RI, Akashi S, Miyake K, Godowski PJ, Tobias PS. Tolllike receptor 4, but not toll-like receptor 2, is a signaling receptor for Escherichia and Salmonella lipopolysaccharides. J Immunol 2004; 165: 5780-5787
  22. Yarovinsky F, Sher A. Toll-like receptor recognition of Toxoplasma gondii. Int J Parasitol 2006; 36: 255-259 https://doi.org/10.1016/j.ijpara.2005.12.003
  23. Campos MA, Almeida IC, Takeuchi O, Akira S, Valente EP, Procopio DO, Travassos LR, Smith JA, Golenbock DT, Gazzinelli RT. Activation of Toll-like receptor-2 by glycosylphosphatidyl-inositol anchors from a protozoan parasite. J Immunol 2001; 167: 416-423 https://doi.org/10.4049/jimmunol.167.1.416
  24. Debierre-Grockiego F, Campos MA, Azzouz N, Schmidt J, Bieker U, Resende MG, Mansur DS, Weingart R, Schmidt RR, Golenbock DT, Gazzinelli RT, Schwarz RT. Activation of TLR2 and TLR4 by glycosylphosphatidylinositols derived from Toxoplasma gondii. J Immunol 2007; 179: 1129-1137 https://doi.org/10.4049/jimmunol.179.2.1129
  25. Mun HS, Aosai F, Norose K, Chen M, Piao L, Takeuchi O, Akira S, Ishikura H, Yano A. TLR2 as an essential molecule for protective immunity against Toxoplasma gondii infection. Int Immunol 2003; 15: 1081-1087 https://doi.org/10.1093/intimm/dxg108
  26. Furuta T, Kikuchi T, Akira S, Watanabe N, Yoshikawa Y. Roles of the small intestine for induction of toll-like receptor 4-mediated innate resistance in naturally acquired murine toxoplasmosis. Int Immunol 2006; 18: 1655-1662 https://doi.org/10.1093/intimm/dxl099
  27. Yarovinsky F, Zhang D, Ansersen JF, Bannenberg GL, Serhan CN, Hayden MS, Hiehy S, Sutterwala FS, Flavell RA, Ghosh S, Sher A. TLR11 activation of dendritic cells by a protozoan profilin- like protein. Science 2005; 308: 1626-1629 https://doi.org/10.1126/science.1109893
  28. Del Rio L, Butcher BA, Bennouna S, Hieny S, Sher A, Denkers EY. Toxoplasma gondii triggers myeloid differentiation factor 88- dependent IL-12 and chemokine ligand 2 (monocyte chemoattractant protein 1) responses using distinct parasite molecules and host receptors. J Immunol 2004; 172: 6954-6960 https://doi.org/10.4049/jimmunol.172.11.6954
  29. Maldonado-Bernal C, Kirschning C, Rosenstein Y, Rocha LM, Rios-Sarabia N, Espinosa-Cantellno M, Becker I, Estrada I, Salazar- Gonzalesz RM, Lopez-Macias C, Wanga H, Sanchez J, Isibasi A. The innate immune response to Entamoeba histolytica lipopeptidophosphoglycan is mediated by toll-like receptors 2 and 4. Parasite Immunol 2005; 27: 127-137 https://doi.org/10.1111/j.1365-3024.2005.00754.x

Cited by

  1. Proinflammatory Cytokine and Nitric Oxide Production by Human Macrophages Stimulated with Trichomonas vaginalis vol.47, pp.3, 2009, https://doi.org/10.3347/kjp.2009.47.3.205
  2. Disparate Regulation of LPS-Induced MAPK Signaling and IL-12p40 Expression Between Different Myeloid Cell Types with and without HIV Infection vol.23, pp.1, 2008, https://doi.org/10.1089/vim.2009.0054
  3. Suppressed CD31 Expression in Sarcoma-180 Tumors after Injection with Toxoplasma gondii Lysate Antigen in BALB/c Mice vol.48, pp.2, 2010, https://doi.org/10.3347/kjp.2010.48.2.171
  4. Suppression of $CD4^+$ T-Cells in the Spleen of Mice Infected with Toxoplasma gondii KI-1 Tachyzoites vol.48, pp.4, 2008, https://doi.org/10.3347/kjp.2010.48.4.325
  5. Possible role of TLR4 and TLR9 SNPs in protection against congenital toxoplasmosis vol.34, pp.10, 2008, https://doi.org/10.1007/s10096-015-2461-3
  6. GSH-C4 Acts as Anti-inflammatory Drug in Different Models of Canonical and Cell Autonomous Inflammation Through NFκB Inhibition vol.10, pp.None, 2008, https://doi.org/10.3389/fimmu.2019.00155
  7. Production of Inflammatory Cytokines and Nitric Oxide by Human Mast Cells Incubated with Toxoplasma gondii Lysate vol.57, pp.2, 2019, https://doi.org/10.3347/kjp.2019.57.2.201
  8. The GRA15 protein from Toxoplasma gondii enhances host defense responses by activating the interferon stimulator STING vol.294, pp.45, 2008, https://doi.org/10.1074/jbc.ra119.009172
  9. The effects of zinc amino acid complex on biomarkers of gut integrity, inflammation, and metabolism in heat-stressed ruminants vol.104, pp.2, 2008, https://doi.org/10.3168/jds.2020-18909