NK cells in hepatitis B virus infection: a potent target for immunotherapy

Abstract

Viruses, including hepatitis B virus (HBV), are the most prevalent and infectious agents that lead to liver disease in humans. Hepatocellular carcinoma (HCC) and cirrhosis of the liver are the most serious complications arising from prolonged forms of hepatitis B. Previous studies demonstrated that patients suffering from long-term HBV infections are unable to eradicate HBV from hepatocytes completely. The mechanisms responsible for progression of these forms of infection have not yet been clarified. However, it seems that there are differences in genetic and immunological parameters when comparing patients to subjects who successfully clear HBV infections, and these may represent the causes of long-term infection. Natural killer (NK) cells, the main innate immune cells that target viral infections, play important roles in the eradication of HBV from hepatocytes. NK cells carry several stimulatory and inhibitor receptors, and binding of receptors with their ligands results in activation and suppression of NK cells, respectively. The aim of this review is to address the recent information regarding NK cell phenotype, functions and modifications in hepatitis B. This review addresses the recent data regarding the roles of NK cells as novel targets for immunotherapies that target hepatitis B infection. It also discusses the potential to reduce the risk of HCC or cirrhosis of the liver by targeting NK cells.

Inflammasomes Coordinate Pyroptosis and Natural Killer Cell Cytotoxicity to Clear Infection by a Ubiquitous Environmental Bacterium

“…These cytotoxic effects require perforin, a pore-forming protein that NK/NKT and cytotoxic T lymphocytes (CTLs) use to kill target cells (Kägi et al, 1994; Lopez et al, 2013). However, while NK and/or NKT cell cytotoxic activity is a well-established antiviral effector mechanism (Shabani et al, 2014), it has not been established as an important defense mechanism against intracellular bacteria. For example, WT and Prf1 −/− mice had similar bacterial burdens after infection with the model intracellular pathogens L. monocytogenes or S. typhimurium (Figure 4I–J and S4B–C).…”

The anti-canine distemper virus activities of ex vivo-expanded canine natural killer cells

“…Recent studies have shown that NK cells play important roles in eradication of viral infections by secreting inflammatory cytokines, especially INF-g, as well as by directly lysing infected cells (Shabani et al, 2014;Zhang et al, 2010). INF-g and TNF-a levels were markedly elevated in NK cell culture supernatants (Fig.…”

“…The effector functions of NK cells are balanced by signals transmitted via activating and inhibitory receptors. The lack of KIR-or Ly49-MHC class I interactions is associated with the potency of NK-mediated target cell killing (Pyzik et al, 2011;Rossini et al, 2012;Shabani et al, 2014;Vidal et al, 2011;Zhang et al, 2010). An additional hypothesis to explain the increased susceptibility of CDV-infected cells to NK cell lysis is that the CDV H protein, which is the major factor determining cell tropism, functions as a ligand for the NCRs NKp30, NKp44, and NKp46.…”

“…Numerous studies have found that human NK cells are important in the immune response to a number of viruses, including influenza virus, vaccinia virus, hepatitis B virus, WNV, HIV-1, and measles virus (Griffin et al, 1990;Johansson et al, 2011;Kottilil et al, 2003;Lin et al, 2012;Shabani et al, 2014;Vidal et al, 2011;Zhang et al, 2010). Additionally, NK cell activation levels are negatively correlated with virus DNA levels in infected patients (Kottilil et al, 2003;Shabani et al, 2014).…”

“…Additionally, NK cell activation levels are negatively correlated with virus DNA levels in infected patients (Kottilil et al, 2003;Shabani et al, 2014). It has also been shown that the number of activated NK cells is markedly increased during the acute phase of measles virus infection The antibody-dependent cellular cytotoxicities (ADCCs) of expanded NK cells against CDV-infected Vero cells.…”