Figure 6. TLR7 and TLR8 expression associated with collagen expression in monocytes during chronic HCV infection.
(A–C) CD14+ monocytes from controls and HCV-infected patients were isolated and the levels of TLR3, TLR7 and TLR8 were determined by PCR. The data is representative of n=5 (Controls) and n=8 (HCV). (D) Monocytes transfected with scrambled or TLR3, TLR7 or TLR8 siRNA for 48 hours and the transfected monocytes were stimulated for 5 days with Huh7.5 or Huh7.5/JFH1 concentrate. The levels of collagen mRNA was measured in the monocytes (E) PBMCs isolated from the controls and HCV-infected patients were immunophenotyped for the presence of fibrocytes (CD14+ pro-Collagen1α+). The data is representative of n=5 (Controls) and n=8 (HCV). (F) Correlation of TLR7 and TLR8 expression with circulating fibrocyte levels of HCV-infected patients (G) Working model of HCV mediated monocyte differentiation and polarization. HCV-infected hepatocytes release virus which interacts with monocytes to induce differentiation into MΦs. These M2-like macrophages secrete both pro- and anti-inflammatory cytokines. Early secretion of IL-1β facilitates the secretion of TGFβ, which leads to HSC activation. In vivo data reveals the presence of M2 marker expressing monocytes in circulation of HCV-infected patients and collagen expressing fibrocytes.