Abstract
BackgroundAnti-hepatitis C virus (HCV) responses are often accompanied by an increase in alanine aminotransferase levels in HCV-infected patients, indicating that inflammatory responses are compromised by the virus. Additionally, inflammation is associated with M1-polarizated macrophages, which secrete cytokines such as tumor necrosis factor-α, interleukin-1, and interleukin-12, and present antigens through phagocytosis. HCV-encoded proteins are presented as specific viral antigens in particular infectious steps that influence the immune response. For instance, HCV antigens impact macrophage PD-1 and Tim-3 expression, and contribute to impaired viral clearance. Furthermore, circulatory HCV antigens from infected patients inhibit dendritic cell differentiation, which raises the possibility that HCV antigens may also interfere with macrophage polarization.MethodsIn this study, the impact of HCV antigen stimulation on M1-polarized macrophages was investigated. The influence of HCV antigens was evaluated by reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay. Specific changes were investigated clinically by flow cytometry and immunofluorescence. Effects of NF-κB during the process were analyzed by western blot.ResultsHCV infection dampened M1 macrophage polarization ex vivo and in vitro. After antigen stimulation, NF-κB signaling was suppressed by the up-regulation of A20 and A20-binding inhibitor of NF-κB binding protein, which likely leads to a variation of functional molecules such as tumor necrosis factor-α, CD163, matrix metalloproteinases, transferrin receptor-1, and CD100, reflecting an anti-inflammatory reaction against M1-polarization.ConclusionHCV antigens stimulation up-regulates A20/A20-binding inhibitor of NF-κB binding protein expression, which consequently contributes to inefficient M1 macrophage polarization.Electronic supplementary materialThe online version of this article (doi:10.1186/s12985-015-0379-0) contains supplementary material, which is available to authorized users.
Highlights
Anti-hepatitis C virus (HCV) responses are often accompanied by an increase in alanine aminotransferase levels in HCV-infected patients, indicating that inflammatory responses are compromised by the virus
In vitro data indicated that HCV antigen exposure to monocytes influenced M1-polarization by decreasing IL-12, CD100 and transferrin receptor-1 (TfR1), as well as up-regulating CD163 and matrix metalloproteinases (MMPs), implying compromised cell polarization
In summary, this study demonstrated that HCV antigens impact M1 macrophage polarization
Summary
Anti-hepatitis C virus (HCV) responses are often accompanied by an increase in alanine aminotransferase levels in HCV-infected patients, indicating that inflammatory responses are compromised by the virus. Inflammation is associated with M1-polarizated macrophages, which secrete cytokines such as tumor necrosis factor-α, interleukin-1, and interleukin-12, and present antigens through phagocytosis. Anti-HCV responses are often accompanied by an increase in alanine aminotransferase (ALT) levels. Patients exhibit persistent mild up-regulated ALT in chronic HCV, indicating that the virus may dampen inflammatory responses. Inflammation is associated with professional antigen presenting cells (APCs) including dendritic cells (DCs) and macrophages that secrete cytokines such as tumor necrosis (TNF)-α and interleukin (IL)-12, and present antigens for T and B cells to facilitate immune responses [2, 3].
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