Increased levels of pDCs and TLR-9 were negatively correlated with HBV DNA, and were thus capable of predicting the IFN-α treatment response in patients with CHB and HBeAg-positive status.
Mechanistically, we show, using human myeloma B cell line RPMI 8226, that the surface Ag hepatitis B surface Ag was responsible for TLR9 dysfunction. hepatitis B surface Ag suppressed the phosphorylation and thus the activation of the transcription factor CREB, preventing TLR9 promoter activity.
The HBV DNA level (IU/ml) was positively correlated with levels of Lnc-DC and TLR9, further demonstrating that Lnc-DC was associated with the immune response of HBV.
A TLR7 agonist is in clinical trials for the treatment of chronic HBV infection while a HBV vaccine using a TLR9 ligand as an adjuvant has proven to be superior to conventional HBV vaccines and has been approved for clinical use.
Targeting the defects in TLR9 or reactivating the downstream pathways that are normally switched on by TLR9 in response to HBV infection is a new approach to the treatment of long-term HBV infection.
Particularly we found that TLR9 mRNA expression is negatively correlated with serum alanine aminotransferase (ALT), Tbil, PTA, and positively correlated with hepatitis B virus (HBV) viral load in CHB patients.