Hepatitis B Immunopathogenesis and Immunotherapy

Abstract

Worldwide there are over 248 million chronic carriers of HBV of whom about a third eventually develop severe HBV-related complications. Due to the major limitations of current therapeutic approaches, the development of more effective strategies to improve therapeutic outcomes in chronic hepatitis B (CHB) patients seems crucial. Immune activation plays a critical role in spontaneous viral control; therefore, new modalities based on stimulation of the innate and adaptive immune responses could result in the resolution of infection and are promising approaches. Here, we summarize the HBV immunopathogenesis, and discuss the encouraging results obtained from the promising immune-based innovations, such as therapeutic vaccination, cytokine therapy, cell-based therapies and blocking inhibitory receptors, as current and future immunotherapeutic interventions.

Immune function of plasmacytoid dendritic cells, natural killer cells, and their crosstalk in HBV infection

“…The majority of studies have shown that there is no significant difference between the frequency of pDCs and mDCs between CHB patients and healthy controls. 15,28,32,33 However, some exceptions exist, some studies showed reduced frequencies of pDC in patients with CHB. [34][35][36] In one study, nucleotide analogue antiviral therapy restored the number of circulating pDC, 34 while another study reported that this treatment improved the number of mDCs, but not of pDCs.…”

“…The majority of studies show that TLR-9 mediated IFN-α production by pDCs of CHB patients is reduced as compared with that of healthy individuals. 15,31,37,40 Besides, TLR9 protein expression levels are remarkably decreased in peripheral blood mononuclear cells (PBMC) from CHB patients reflecting dramatic shut down of TLR9 in both pDC and B cells. 31 In spite of the inhibitory effect of HBV/HBsAg on TLR9 stimulation, HBV/HBsAg exerts no effect on TLR7-mediated IFN-α secretion.…”

“…Despite efficient internalization of HBV virions and presence of subviral particles within pDCs, there is a dysfunctional response of pDC to TLR9-L stimulation, which is not associated with the viral load, 15 and also is not caused by induction of cell apoptosis. 31 Likewise, it has also been shown that neither HBV nor its viral proteins reduce pDC viability.…”

“…By changing pDC functions and disrupting the interaction between pDC and NK cells, HBV can escape antiviral immunity. 15 Understanding the mechanisms by which HBV suppresses or attenuates the activity of pDCs, NK cells and their crosstalk provides insight to improve new immunotherapeutic approaches for treatment of chronic HBV infection (CHB). 16 Many review articles have so far been published which discuss the role of different immune cells in controlling acute and chronic HBV infections.…”

Antibiotic susceptibility and plasmid profi le of heavy metal resistant Pseudomonas species

“…The HBV is now a challenging global health related issue especially in the Asia Pacifi c region. Both the host and the viral factors are mainly said to be associated to the pathogenesis of HBV infection, which are known to contribute to the clinical outcomes of chronic HBV infection Liver diseases and liver cancer shows a marked worldwide geographic and ethnic distribution (Shields and Harris, 1991, Lee et al,1997, Liu, Chen and Lai, 2003and Golsaz and Shokri 2016.…”