Skip to main content
SpringerLink
Log in

Expression of toll-like receptor 9 in peripheral blood mononuclear cells from patients with different hepatitis B and C viral loads

  • Published:
Journal of Huazhong University of Science and Technology [Medical Sciences] Aims and scope Submit manuscript

Summary

The aim of the present study was to investigate the expression of toll-like receptors (TLR) 9 in peripheral blood mononuclear cells (PBMC) of patients with chronic hepatitis B and C with different virus copies. The study group included 90 patients (60 with chronic hepatitis B, and 30 with chronic hepatitis C), and 20 healthy people served as control group. The protein and mRNA levels of TLR9 were detected by using flow cytometry and real-time PCR. The serum viral copies of HBV and HCV were measured in all patients, and the correlation between HBV-DNA copies or HCV-RNA copies and the TLR9 expression was analyzed. Our results demonstrated that HBV or HCV infection led to a decreased expression of TLR9 mRNA and protein compared to the control group (P<0.05). The TLR9 protein and mRNA levels were negatively correlated with serum viral copies of HBV and HCV (r=−0.632, r=−0.909, P<0.01). It was concluded that TLR9 mRNA and protein are down-regulated in PBMC of HBV-infected or HCV-infected patients, and they are negatively correlated with serum viral copies and play an important role in detecting viral replication of HBV and HCV.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Refeences

  1. Visvanathan K, Lewin SR. Immunopathogenesis: role of innate and adaptive immune responses. Semin Liver Dis, 2006,26:104–115

    Article  PubMed  CAS  Google Scholar 

  2. Chisari FV, Ferrari C. Hepatitis B virus immunopathogenesis. Annu Rev Immunol, 1995,13:29–60

    Article  PubMed  CAS  Google Scholar 

  3. Moriishi K, Matsuura Y. Mechanisms of hepatitis C virus infection. Antivir Chem Chemother, 2003,14(6):285–297

    PubMed  CAS  Google Scholar 

  4. Cerny A, McHutchison J G, Pasquinelli C, et al. Cytotoxic T lymphocyte response to hepatitis C virus-derived peptides containing the HLA A2.1 binding motif. J Clin Investig, 1995,95:521–530

    Article  PubMed  CAS  Google Scholar 

  5. Lechner F, Wong D K, Dunbar P R, et al. Analysis of successful immune responses in persons infected with hepatitis C virus. J Exp Med, 2000, 191:1499–1512

    Article  PubMed  CAS  Google Scholar 

  6. Shoukry N H, Grakoui A, Houghton M, et al. Memory CD8 T cells are required for protection from persistent hepatitis C virus infection. J Exp Med, 2003,197:1645–1655

    Article  PubMed  CAS  Google Scholar 

  7. Thimme R, Oldach D, Chang K M, et al. Determinants of viral clearance and persistence during acute hepatitis C virus infection. J Exp Med, 2001,194:1395–1406

    Article  PubMed  CAS  Google Scholar 

  8. Takeda K, Kaisho T, Akira S. Toll-like receptors. Ann Rev Immunol, 2003,21:335–337

    Article  CAS  Google Scholar 

  9. Medzhitov R, Janeway C Jr. Innate immune recognition: mechanisms and pathways. Immunol Rev, 2000,173:89–97

    Article  PubMed  CAS  Google Scholar 

  10. Werling D, Jungi TW. Toll-like receptors linking innate and adaptive immune response. Vet Immunol Immunopathol, 2003,91:1–12

    Article  PubMed  CAS  Google Scholar 

  11. Takeda K, Akira S. Toll-like receptors in innate immunity. Int Immunol, 2005,17:1–14

    Article  PubMed  CAS  Google Scholar 

  12. Janeway CA Jr, Medzhitov R. Innate immune recognition. Annu Rev Immunol, 2002,20:197–216

    Article  PubMed  CAS  Google Scholar 

  13. Iwasaki A, Medzhitov R. Toll-like receptor control of the adaptive immune responses. Nat Immunol, 2004,5:987–995

    Article  PubMed  CAS  Google Scholar 

  14. Hornung V, Rothenfusser S, Britsch S, et al. Quantitative expression of toll-like receptor 1–10 mRNA in cellular subsets of human peripheral blood mononuclear cells and sensitivity to CpG oligodeoxynucleotides. J Immunol, 2002,168:4531–4537

    PubMed  CAS  Google Scholar 

  15. Schlaepfer E, Audige A, Joller H, et al. TLR7/8 triggering exerts opposing effects in acute versus latent HIV infection. J Immunol, 2006,176:2888–2895

    PubMed  CAS  Google Scholar 

  16. Ito T, Wang YH, Liu YJ. Plasmacytoid dendritic cell precursors/type I interferon-producing cells sense viral infection by Toll-like receptor (TLR) 7 and TLR9. Springer Semin Immunopathol, 2005,26:221–229

    Article  PubMed  CAS  Google Scholar 

  17. Yang K, Puel A, Zhang S, et al. Human TLR-7-, -8-, and -9-mediated induction of IFN-alpha/beta and -lambda is IRAK-4 dependent and redundant for protective immunity to viruses. Immunity, 2005,23:465–478

    Article  PubMed  CAS  Google Scholar 

  18. Krug A, Luker GD, Barchet W, et al. Herpes simplex virus type 1 activates murine natural interferon-producing cells through toll-like receptor 9. Blood, 2004, 103:1433–1437

    Article  PubMed  CAS  Google Scholar 

  19. Andersen JM, Al-Khairy D, Ingalls RR. Innate immunity at the mucosal surface: role of toll-like receptor 3 and toll-like receptor 9 in cervical epithelial cell responses to microbial pathogens. Biol Reprod, 2006,74:824–831

    Article  PubMed  CAS  Google Scholar 

  20. Huang YH, Chou MH, Du YY, et al. Expression of toll-like receptors and type 1 interferon specific protein MxA in biliary atresia. Lab Invest, 2006,87:66–74

    Article  PubMed  Google Scholar 

  21. Lesmeister MJ, Bothwell MR, Misfeldt ML. Toll-like receptor expression in the human nasopharyngeal tonsil (adenoid) and palantine tonsils: a preliminary report. Int J Pediatr Otorhinolaryngol, 2006, 70:987–992

    Article  PubMed  Google Scholar 

  22. Chinese Society of Hepatology and Chinese Society of Infectious Diseases CMA. The guideline of prevention and treatment for chronic hepatitis B. Chin J Hepatol (Chinese), 2005,13:881–890

    Google Scholar 

  23. Ross JW, Ashworth MD, Hurst AG, et al. Analysis and characterization of differential gene expression during rapid trophoblastic elongation in the pig using suppression subtractive hybridization. Reprod Biol Endocrinol, 2003,1:23

    Article  PubMed  Google Scholar 

  24. Chuang TH, Ulevitch RJ. Cloning and characterization of a subfamily of human toll-like receptors: hTLR7, hTLR8 and hTLR9. Eur Cytokine Netw, 2000,11:372–378

    PubMed  CAS  Google Scholar 

  25. Du X, Poltorak A, Wei Y, et al. Three novel mammalian toll-like receptors: gene structure, expression, and evolution. Eur Cytokine Netw, 2000,11:362–371

    PubMed  CAS  Google Scholar 

  26. Isogawa M, Robek MD, Furuichi Y, et al. Toll-like receptor signaling inhibits hepatitis B virus replication in vivo. J Virol, 2005,79:7269–7272

    Article  PubMed  CAS  Google Scholar 

  27. An H, Xu H, Yu Y, et al. Up-regulation of TLR9 gene expression by LPS in mouse macrophages via activation of NF-kappaB, ERK and p38 MAPK signal pathways. Immunol Lett, 2002,81:165–169

    Article  PubMed  CAS  Google Scholar 

  28. McKimmie CS, Johnson N, Fooks AR, et al. Viruses selectively upregulate Toll-like receptors in the central nervous system. Biochem Biophys Res Commun, 2005, 336:925–933

    Article  PubMed  CAS  Google Scholar 

  29. Bauer S. Toll-erating self DNA. Nat Immunol, 2006,7: 13–15

    Article  PubMed  CAS  Google Scholar 

  30. Barton GM, Kagan JC, Medzhitov R. Intracellular localization of Toll-like receptor 9 prevents recognition of self DNA but facilitates access to viral DNA. Nat Immunol, 2006,7:49–56

    Article  PubMed  CAS  Google Scholar 

  31. Schmausser B, Andrulis M, Endrich S, et al. Expression and subcellular distribution of toll-like receptors TLR4, TLR5 and TLR9 on the gastric epithelium in Helicobacter pylori infection. Clin Exp Immunol, 2004,136: 521–526

    Article  PubMed  CAS  Google Scholar 

  32. Lee J, Rachmilewitz D, Raz E. Homeostatic effects of TLR9 signaling in experimental colitis. Ann N Y Acad Sci, 2006,1072:351–355

    Article  PubMed  CAS  Google Scholar 

  33. Eaton-Bassiri A, Dillon SB, Cunningham M, et al. Toll-like receptor 9 can be expressed at the cell surface of distinct populations of tonsils and human peripheral blood mononuclear cells. Infect Immun, 2004,72:7202–7211

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Infectious Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Jian Zhou  (周 健), Yuancheng Huang  (黄元成), Deying Tian  (田德英), Dong Xu  (许 东), Miao Chen  (陈 淼) & Huiling Wu  (吴会玲)

Authors
  1. Jian Zhou  (周 健)
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yuancheng Huang  (黄元成)
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Deying Tian  (田德英)
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dong Xu  (许 东)
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Miao Chen  (陈 淼)
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Huiling Wu  (吴会玲)
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

This project was supported by a grant from Natural Sciences Foundation of Hubei Province, China (No. 2006ABA139).

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhou, J., Huang, Y., Tian, D. et al. Expression of toll-like receptor 9 in peripheral blood mononuclear cells from patients with different hepatitis B and C viral loads. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 29, 313–317 (2009). https://doi.org/10.1007/s11596-009-0310-2

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11596-009-0310-2

Key words

Search

Navigation