Hepatitis B virus surface antigen impairs myeloid dendritic cell function: a possible immune escape mechanism of hepatitis B virus
| Autor: | Andrea M. Woltman, Renate G. van der Molen, Rekha S. Binda, Harry L.A. Janssen, Mark H van Roosmalen, Ulrike Protzer, Marjoleine L. Op den Brouw |
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| Přispěvatelé: | Gastroenterology & Hepatology, Immunology |
| Rok vydání: | 2009 |
| Předmět: |
Adult
Male HBsAg Hepatitis B virus Myeloid T-Lymphocytes Immunology Biology medicine.disease_cause Lymphocyte Activation Auto-immunity transplantation and immunotherapy [N4i 4] T-Lymphocytes Regulatory Virus Young Adult Immune system SDG 3 - Good Health and Well-being Antigen Immunity medicine Immune Tolerance Immunology and Allergy Humans CD40 Antigens Cells Cultured Hepatitis B Surface Antigens virus diseases Original Articles Dendritic Cells Middle Aged Virus Internalization medicine.disease Virology Interleukin-12 digestive system diseases Up-Regulation medicine.anatomical_structure B7-1 Antigen Female B7-2 Antigen Lymphocyte Culture Test Mixed Viral hepatitis |
| Zdroj: | Immunology, 126, 280-9 Immunology, 126, 2, pp. 280-9 Immunology, 126(2), 280-289. Wiley-Blackwell Publishing Ltd |
| ISSN: | 0019-2805 |
| Popis: | Item does not contain fulltext Chronic hepatitis B virus (HBV) infection is the result of an inadequate immune response towards the virus. Myeloid dendritic cells (mDC) of patients with chronic HBV are impaired in their maturation and function, resulting in more tolerogenic rather than immunogenic responses, which may contribute to viral persistence. The mechanism responsible for altered mDC function remains unclear. The HBV-infected patients display large amounts of HBV particles and viral proteins in their circulation, especially the surface antigen HBsAg, which allows multiple interactions between the virus, its viral proteins and DC. To assess whether HBV directly influences mDC function, the effects of HBV and HBsAg on human mDC maturation and function were investigated in vitro. As already described for internalization of HBV by DC, the present study shows that peripheral blood-derived mDC of healthy controls also actively take up HBsAg in a time-dependent manner. Cytokine-induced maturation in the presence of HBV or HBsAg resulted in a significantly more tolerogenic mDC phenotype as demonstrated by a diminished up-regulation of costimulatory molecules and a decreased T-cell stimulatory capacity, as assessed by T-cell proliferation and interferon-gamma production. In addition, the presence of HBV significantly reduced interleukin-12 production by mDC. These results show that both HBV particles and purified HBsAg have an immune modulatory capacity and may directly contribute to the dysfunction of mDC in patients with chronic HBV. The direct immune regulatory effect of HBV and circulating HBsAg particles on the function of DC can be considered as part of the mechanism by which HBV escapes immunity. |
| Databáze: | OpenAIRE |
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