Contribution of Toll-like receptors to the control of hepatitis B virus infection by initiating antiviral innate responses and promoting specific adaptive immune responses

• Published in: Cellular & molecular immunology Vol. 12; no. 3; pp. 273 - 282
• Main Authors: Ma, Zhiyong, Zhang, Ejuan, Yang, Dongliang, Lu, Mengji
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-05-2015; Nature Publishing Group
• Subjects: Adaptive Immunity; Animals; Antibodies; Antigens, Viral - immunology; Antiviral Agents - pharmacology; Antiviral Agents - therapeutic use; B-Lymphocytes - immunology; B-Lymphocytes - virology; Biomedical and Life Sciences; Biomedicine; Chronic infection; Cytokines; Drug Therapy, Combination; Hepatitis B; Hepatitis B virus; Hepatitis B virus - physiology; Hepatitis B, Chronic - drug therapy; Hepatitis B, Chronic - immunology; Humans; Immune clearance; Immune response; Immunity, Innate; Immunology; Immunomodulation; Infections; Inflammation; Innate immunity; Interferon; Interferons - immunology; Lymphocytes B; Medical Microbiology; Microbiology; Mini Review; Signal Transduction; T-Lymphocytes - immunology; T-Lymphocytes - virology; Toll-like receptors; Toll-Like Receptors - agonists; Toll-Like Receptors - immunology; Toll样受体; Vaccine; Virus Replication - drug effects; 乙肝; 免疫应答; 抗病毒治疗; 抗病毒药; 控制; 病毒感染; 适应性; Toll like receptor; Adaptive immune response; Hepatitis B virus; Innate immune response
• ISSN: 1672-7681; 2042-0226
• DOI: 10.1038/cmi.2014.112

It is well accepted that adaptive immunity plays a key role in the control of hepatitis B virus （HBV） infection. In contrast, the contribution of innate immunity has only received attention in recent years. Toll-like receptors （TLRs） sense pathogen-associated molecule patterns and activate antiviral mechanisms, including intracellular antiviral pathways and the production of antiviral effector interferons （IFNs） and pro-inflammatory cytokines. Experimental results from in vitroand in vivo models have demonstrated that TLRs mediate the activation of cellular signaling pathways and the production of antiviral cytokines, resulting in a suppression of HBV replication. However, HBV infection is associated with downregulation of TLR expression on host cells and blockade of the activation of downstream signaling pathways. In primary HBV infection, TLRs may slow down HBV infection, but contribute only indirectly to viral clearance. Importantly, TLRs may modulate HBV-specific T- and B-cell responses in vivo, which are essential for the termination of HBV infection. Thus, TLR agonists are promising candidates to act as immunomodulators for the treatment of chronic HBV infection. Antiviral treatment may recover TLR expression and function in chronic HBV infection and may increase the efficacy of therapeutic approaches based on TLR activation. A combined therapeutic strategy with antiviral treatment and TLR activation could facilitate the restoration of HBV-specific immune responses and thereby, achieve viral clearance in chronically infected HBV patients.