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Downregulation of TLR7/9 leads to deficient production of IFN-α from plasmacytoid dendritic cells in chronic hepatitis B.
Inflamm Res. 2012 Sep; 61(9):997-1004.IR

Abstract

OBJECTIVE

To investigate whether Toll-like receptor (TLR) 7 and TLR9-mediated interferon α (IFN-α) production in plasmacytoid dendritic cells (pDCs) is compromised in patients with chronic hepatitis B virus (HBV) infection.

MATERIALS AND METHODS

Peripheral blood mononuclear cells (PBMCs) were prepared from 32 chronic HBV patients and 13 healthy volunteers, and treated with loxoribine or cytidine phosphate guanosine (CpG) oligodeoxynucleotides (ODN). Interferon α in the supernatant was measured by sandwich ELISA. PDC frequency and the expression levels of TLR7 and TLR9 in pDCs were quantified by flow cytometry. The serum viral load of HBV was quantified using a highly sensitive real-time PCR kit.

RESULTS

Compared to cells from healthy control group, PBMCs and pDCs from the HBV group showed significantly decreased production of IFN-α in response to ligand for TLR7 (loxoribine) and TLR9 (CpG ODN, P < 0.05). Mechanistically, the number of pDCs in peripheral blood, and the expression of pDC-associated TLR7 and TLR9 were significantly lower in HBV group than in the healthy control group (P < 0.05). In addition, the number of pDCs and the expression of TLR9 on pDCs were correlated inversely with the serum load of HBV.

CONCLUSION

Impaired IFN-α production from pDC may contribute to the immunopathogenesis of chronic HBV infection, which may be the result of a reduced amount of pDCs as well as decreased expression of TLR7 and TLR9 on pDCs.

Authors+Show Affiliations

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Institute of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310031, China. xuning@zjut.edu.cnNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22684144

Citation

Xu, Ning, et al. "Downregulation of TLR7/9 Leads to Deficient Production of IFN-α From Plasmacytoid Dendritic Cells in Chronic Hepatitis B." Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.], vol. 61, no. 9, 2012, pp. 997-1004.
Xu N, Yao HP, Lv GC, et al. Downregulation of TLR7/9 leads to deficient production of IFN-α from plasmacytoid dendritic cells in chronic hepatitis B. Inflamm Res. 2012;61(9):997-1004.
Xu, N., Yao, H. P., Lv, G. C., & Chen, Z. (2012). Downregulation of TLR7/9 leads to deficient production of IFN-α from plasmacytoid dendritic cells in chronic hepatitis B. Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.], 61(9), 997-1004. https://doi.org/10.1007/s00011-012-0493-z
Xu N, et al. Downregulation of TLR7/9 Leads to Deficient Production of IFN-α From Plasmacytoid Dendritic Cells in Chronic Hepatitis B. Inflamm Res. 2012;61(9):997-1004. PubMed PMID: 22684144.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Downregulation of TLR7/9 leads to deficient production of IFN-α from plasmacytoid dendritic cells in chronic hepatitis B. AU - Xu,Ning, AU - Yao,Hang-Ping, AU - Lv,Guo-Cai, AU - Chen,Zhi, Y1 - 2012/06/10/ PY - 2009/10/11/received PY - 2012/05/09/accepted PY - 2012/01/15/revised PY - 2012/6/12/entrez PY - 2012/6/12/pubmed PY - 2013/1/4/medline SP - 997 EP - 1004 JF - Inflammation research : official journal of the European Histamine Research Society ... [et al.] JO - Inflamm. Res. VL - 61 IS - 9 N2 - OBJECTIVE: To investigate whether Toll-like receptor (TLR) 7 and TLR9-mediated interferon α (IFN-α) production in plasmacytoid dendritic cells (pDCs) is compromised in patients with chronic hepatitis B virus (HBV) infection. MATERIALS AND METHODS: Peripheral blood mononuclear cells (PBMCs) were prepared from 32 chronic HBV patients and 13 healthy volunteers, and treated with loxoribine or cytidine phosphate guanosine (CpG) oligodeoxynucleotides (ODN). Interferon α in the supernatant was measured by sandwich ELISA. PDC frequency and the expression levels of TLR7 and TLR9 in pDCs were quantified by flow cytometry. The serum viral load of HBV was quantified using a highly sensitive real-time PCR kit. RESULTS: Compared to cells from healthy control group, PBMCs and pDCs from the HBV group showed significantly decreased production of IFN-α in response to ligand for TLR7 (loxoribine) and TLR9 (CpG ODN, P < 0.05). Mechanistically, the number of pDCs in peripheral blood, and the expression of pDC-associated TLR7 and TLR9 were significantly lower in HBV group than in the healthy control group (P < 0.05). In addition, the number of pDCs and the expression of TLR9 on pDCs were correlated inversely with the serum load of HBV. CONCLUSION: Impaired IFN-α production from pDC may contribute to the immunopathogenesis of chronic HBV infection, which may be the result of a reduced amount of pDCs as well as decreased expression of TLR7 and TLR9 on pDCs. SN - 1420-908X UR - https://www.unboundmedicine.com/medline/citation/22684144/Downregulation_of_TLR7/9_leads_to_deficient_production_of_IFN_α_from_plasmacytoid_dendritic_cells_in_chronic_hepatitis_B_ L2 - https://dx.doi.org/10.1007/s00011-012-0493-z DB - PRIME DP - Unbound Medicine ER -