The Good and the Bad of Natural Killer Cells in Virus Control: Perspective for Anti-HBV Therapy

• Published in: International journal of molecular sciences 2019-10, Vol.20 (20), p.5080
• Main Authors: Fisicaro, Paola, Rossi, Marzia, Vecchi, Andrea, Acerbi, Greta, Barili, Valeria, Laccabue, Diletta, Montali, Ilaria, Zecca, Alessandra, Penna, Amalia, Missale, Gabriele, Ferrari, Carlo, Boni, Carolina
• Format: Article
• Language: English
• Subjects: Adaptive immunity; Antigens; Antiviral agents; Antiviral Agents - therapeutic use; Cancer; CD4-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - immunology; Chemokines; Chronic infection; Cytokines; Cytokines - metabolism; Cytolytic activity; Cytotoxicity; Gene expression; Hepatitis B; Hepatitis B virus - immunology; Hepatitis B, Chronic - drug therapy; Hepatitis B, Chronic - immunology; Humans; Immunotherapy; Infections; Killer Cells, Natural - enzymology; Killer Cells, Natural - immunology; Ligands; Liver; Lymphocyte Activation - immunology; Lymphocytes; Lymphocytes T; Metabolism; Natural killer cells; Review; Viral infections; Viruses
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20205080

Immune modulatory therapies are widely believed to represent potential therapeutic strategies for chronic hepatitis B infection (CHB). Among the cellular targets for immune interventions, Natural Killer (NK) cells represent possible candidates because they have a key role in anti-viral control by producing cytokines and by exerting cytotoxic functions against virus-infected cells. However, in patients with chronic hepatitis B, NK cells have been described to be more pathogenic than protective with preserved cytolytic activity but with a poor capacity to produce anti-viral cytokines. In addition, NK cells can exert a regulatory activity and possibly suppress adaptive immune responses in the setting of persistent viral infections. Consequently, a potential drawback of NK-cell targeted modulatory interventions is that they can potentiate the suppressive NK cell effect on virus-specific T cells, which further causes impairment of exhausted anti-viral T cell functions. Thus, clinically useful NK-cell modulatory strategies should be not only suited to improve positive anti-viral NK cell functions but also to abrogate T cell suppression by NK cell-mediated T cell killing. This review outlines the main NK cell features with a particular focus on CHB infection. It describes different mechanisms involved in NK-T cell interplay as well as how NK cells can have positive anti-viral effector functions and negative suppressive effects on T cells activity. This review discusses how modulation of their balance can have potential therapeutic implications.