Immunopathology of Chronic Hepatitis B Infection: Role of Innate and Adaptive Immune Response in Disease Progression - PubMed (original) (raw)

Review

Immunopathology of Chronic Hepatitis B Infection: Role of Innate and Adaptive Immune Response in Disease Progression

Arshi Khanam et al. Int J Mol Sci. 2021.

Abstract

More than 250 million people are living with chronic hepatitis B despite the availability of highly effective vaccines and oral antivirals. Although innate and adaptive immune cells play crucial roles in controlling hepatitis B virus (HBV) infection, they are also accountable for inflammation and subsequently cause liver pathologies. During the initial phase of HBV infection, innate immunity is triggered leading to antiviral cytokines production, followed by activation and intrahepatic recruitment of the adaptive immune system resulting in successful virus elimination. In chronic HBV infection, significant alterations in both innate and adaptive immunity including expansion of regulatory cells, overexpression of co-inhibitory receptors, presence of abundant inflammatory mediators, and modifications in immune cell derived exosome release and function occurs, which overpower antiviral response leading to persistent viral infection and subsequent immune pathologies associated with disease progression towards fibrosis, cirrhosis, and hepatocellular carcinoma. In this review, we discuss the current knowledge of innate and adaptive immune cells transformations that are associated with immunopathogenesis and disease outcome in CHB patients.

Keywords: CHB; adaptive immune cells; inflammation; innate immune cells.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1

Innate and adaptive immune system derives pathology in CHB. Chronic HBV infection activates different cellular pathways including the innate and adaptive immune system leading to inflammatory cytokine secretion that aggravate inflammation and hepatic injury. To control the excessive inflammation, expansion of regulatory cells comprising, DCregs, MDSCs, Tregs, and Bregs takes place that produce anti-inflammatory cytokines and other components that cause impaired effector function and immune tolerance. Moreover, both innate and adaptive immune cells over express inhibitory receptors and apoptosis inducing receptors and ligands driving immune exhaustion and cell death. HBV: Hepatitis B virus, DCregs: Regulatory dendritic cells, MDSCs: Myeloid derived suppressor cells, Tregs: Regulatory T cells, NK cells: Natural killer cells, TIM-3: T cell immunoglobulin and mucin-domain containing-3, TIGIT: T cell immunoreceptor with Ig and ITIM domain,PD-1: Programmed death-1, TRAIL: Tumor necrosis factor-related apoptosis-inducing ligand, FASL: FAS ligand, FAS-R: FAS receptor, CTLA-4: Cytotoxic T-lymphocyte antigen 4, Arg1: Arginase-1, PD-L1: Programmed death-ligand 1, PGE2: Prostaglandin E2, iNOS: Inducible nitric oxide synthase, ROS: Reactive oxygen species, IDO: Indoleamine-2,3-dioxygenase.

Figure 2

Innate and adaptive immune cells are involved in hepatic inflammation, fibrosis, cirrhosis, and HCC in CHB. Continuous viral exposure prompts the activation of intrahepatic immune cells that initiates the recruitment of circulating immunocytes to the liver. These infiltrated cells stimulate other parenchymal and non-parenchymal cells in the liver. Th17 cells secrete enormous amounts of IL-17 that bind to its receptor present on the surface of many intrahepatic cells and worsen hepatic inflammation by triggering the inflammatory cascade. Induction of profibrogenic mediators IL-10 and TGF-β encourage liver fibrosis by activating hepatic stellate cells. Moreover, continuous supplementation of these fibrogenic stimuli promotes further disease progression towards fibrosis, cirrhosis, and HCC. MǾ: Macrophage, Th17: T helper 17, KCs: Kupffer cells, HSCs: Hepatic stellate cells, TNF-α: Tumor necrosis factor-α, TGF-β: Transforming growth factor- β, CXCL8: Chemokine ligand 8, HCC: Hepatocellular carcinoma.

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Immunopathology of Chronic Hepatitis B Infection: Role of Innate and Adaptive Immune Response in Disease Progression - PubMed (original) (raw)