Hepatitis C Virus E2 Envelope Glycoprotein Induces an Immunoregulatory Phenotype in Macrophages.
Hepatology
; 69(5): 1873-1884, 2019 05.
Article
em En
| MEDLINE
| ID: mdl-29443378
ABSTRACT
A comprehensive strategy to control hepatitis C virus (HCV) infection needs a vaccine. Our phase I study with recombinant HCV E1/E2 envelope glycoprotein (EnvGPs) as a candidate vaccine did not induce a strong immune response in volunteers. We analyzed the interactions of HCV EnvGPs with human monocyte-derived macrophages as antigen-presenting cells. HCV E2 induced immune regulatory cytokine interleukin (IL)-10 and soluble CD163 (sCD163) protein expression in macrophages from 7 of 9 blood donors tested. Furthermore, HCV E2 enhanced Stat3 and suppressed Stat1 activation, reflecting macrophage polarization toward M2 phenotype. E2-associated macrophage polarization appeared to be dependent of its interaction with CD81 leading endothelial growth factor receptor (EGFR) activation. Additionally, E2 suppressed the expression of C3 complement, similar to HCV-exposed dendritic cells (DCs), implying potential impairment of immune cell priming. Conclusion:
Our results suggest that E2 EnvGP may not be an ideal candidate for HCV vaccine development, and discrete domains within E2 may prove to be more capable of elliciting a protective immune response. (Hepatology 2018).
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas do Envelope Viral
/
Interações Hospedeiro-Patógeno
/
Macrófagos
Limite:
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article