Ribavirin Improves NK Cell IFNγ Response During Sofosbuvir-based DAA Therapy in HCV-infected Liver Transplant Recipients

Abstract

This study was supported by grant We-4675/3-1 from the Deutsche Forschungsgemeinschaft (DFG),

Elevated CD56brightNK cell and IFNγ levels in the blood of children with common cold provides a clue for preventing COVID-19

“…We have also observed a linear positive correlation between CD56 bright NK cells and IFNγ levels in the blood of children. CD56 bright NK cells primarily regulate immune responses by secreting a large number of cytokines [37], and previous studies have indicated that these cells secrete IFNγ to combat viral infections [38,39]. Therefore, we hypothesize that the elevated levels of CD56 bright NK cells in children's blood contribute to the production of IFNγ, which serves as a protective response against common cold virus infection.…”

Immunomodulation of Natural Killer Cell Function by Ribavirin Involves TYK-2 Activation and Subsequent Increased IFN-γ Secretion in the Context of In Vitro Hepatitis E Virus Infection

“…Where stated, cells were stimulated with combinations of recombinant human IL-12 (R&D Systems, Minneapolis, MN, USA), IL-15 (R&D Systems), and IL-18 (R&D Systems) for 12 h at concentrations of 0.5 ng/mL, 20 ng/mL, and 100 ng/mL [24,25,29,30], respectively, and protein transport inhibitors containing brefeldin A (BD Biosciences, Franklin Lakes, WI, USA) and monensin (BD Biosciences) were added for the last 4 h. For analyzing CD107a degranulation, cells were stimulated with K562 cells (ATCC, Manassas, VA, USA) at an effector to target ratio of 1:1 and anti-CD107a was added during the last 6 h.…”

“…Liver biopsies revealed that especially in severe cases, HEV-infected patients show the highest numbers of intrahepatic NK cells compared to other viral hepatitis [22]. Previous studies have shown that RBV treatment in the setting of HCV infection results in an enhanced NK cell IFN-γ response [24,25]. However, the exact mechanism remains unclear.…”

Ribavirin to the Rescue: Natural Killer–Cell Function After Hepatitis C Virus Treatment in Liver Transplant Recipients

“…This reproduces what others have demonstrated that despite elimination of constitutive IFN-α signaling from HCV clearance, some chronic NK-cell functional changes persist. However, in the chronic HCV-infected liver transplant recipients who received treatment with ribavirin, Adenugba et al 6 show that there was an increase in frequency of IFN-γ capacity in NK cells, most notably in an activated population, which correlated to an increase in phosphorylated STAT4. These findings were notably absent in recipients who did not receive ribavirin as part of the HCV treatment protocol, suggesting an immunomodulatory effect of ribavirin independent of HCV clearance.…”

“…In this issue of Transplantation , Adenugba et al 6 report that HCV-infected liver transplant recipients had similarly skewed NK-cell function with increased CD107a, a measure of cytotoxicity, and reduced IFN-γ capacity compared with HCV-uninfected liver transplant recipients. The authors demonstrated that in vitro IFN-α stimulation reproduced altered signal transducer and activator of transcription (STAT) signaling in NK cells from HCV-infected liver transplant recipients (Figure 1B).…”