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Exosomes: multitask cargo carriers modulating innate immunity to viruses

Cellular & Molecular Immunology volume 14, pages 476–477 (2017)Cite this article

Chronic infection with hepatitis B virus (HBV) is a major cause of cirrhosis and liver cancer worldwide. HBV is a smart DNA virus that replicates through an RNA intermediate. The viral genome translocates to the nucleus where it is converted into covalently closed circular DNA (cccDNA) serving as a template for viral transcription.1 Acute HBV infection is usually self-limited in adults but HBV cccDNA may persist for life in the host’s hepatocytes as a mini-chromosome often resulting in occult infection, which may reactivate in case of immune suppression. Although HBV eradication is theoretically possible, there are currently no drugs capable of achieving complete viral clearance when chronic infection is established. Viral control occurs through coordinated innate2 and adaptive3 immune responses. Although the latter are thought to be instrumental in getting to grips with most viral infections including HBV, the former, that were traditionally viewed as having a critical role in the initial containment of viraemia in acute infections, are now gaining substantial credit as fine tuners of T-cell responses to regulate immunopathology. Moreover, the rigid partition between the two branches of immune responses is losing ground as cells traditionally assigned to innate immunity, such as natural killer (NK) cells, have been shown to bear classical adaptive features such as long-lived memory or fine specificity.4

NK cells represent a cornerstone in the defense against pathogens and are tightly regulated by several membrane receptors able to switch the NK function toward activation or inhibition after ligand recognition and interaction.5 Their ability to contribute to control HBV has been clearly demonstrated in humans;6 however, during chronic HBV infection, multiple studies have shown that NK cells are defective in the production of cytokines, such as interferon-γ (IFNγ) and tumor necrosis factor-α, impairing their non-cytolytic antiviral capacity.7 In addition, NK cells fulfill negative tasks in chronic HBV infection by inhibiting antiviral T-cell responses, via rapid, contact-dependent killing of HBV-specific T cells.8 Further, NK-cell depletion as well as TNF-related apoptosis-inducing ligand and the NK group 2D pathway blockade improves HBV-specific T-cell function, providing incremental evidence for a critical role of NK cells in HBV infection.9

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  1. Department of Infectious Diseases, and Department of Internal Medicine and Therapeutics, Research Laboratories, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, 27100, Italy

    Mario U Mondelli

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Mondelli, M. Exosomes: multitask cargo carriers modulating innate immunity to viruses. Cell Mol Immunol 14, 476–477 (2017). https://doi.org/10.1038/cmi.2016.27

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