[23] While little is known of the role of NKT cells in acute HCV infection, NK cells have been a focus of research in recent years.[24] In accordance with many of these studies[15, 25] we observed changes in the expression level of multiple NK markers. Among those, the transient up-regulation

of the inhibitory receptor NKG2A on NK cells of HCV-exposed healthcare workers without detectable viremia is of note, because it has been shown to correlate inversely with HCV RNA levels in chronic HCV infection.[25, 26] Furthermore, as in chronic HCV infection,[15, 27] NK cells displayed an activated and cytotoxic phenotype as determined by increased Ferroptosis inhibitor TRAIL expression and NK cell degranulation in response to MHC class I-negative target cells. TRAIL-mediated cytotoxicity appears to be a relevant antiviral mechanism because Selleck Etoposide in vitro activated NK cells have been shown to kill HCV-infected hepatoma cells in a TRAIL-dependent manner,[28] and because HCV infection increases the sensitivity of primary human hepatocytes to TRAIL-mediated killing.[29] Increased IFN-γ production by NK cells has also been described in acute HCV infection[12, 13] but is decreased in chronic HCV infection.[15, 27] This is reminiscent of a mouse model of infection

with a hepatotropic virus (lymphocytic choriomeningitis virus) where NK cells produce IFN-γ immediately after infection but lose this capacity when high-level viremia persists.[30] Thus, IFN-γ production may be an important component of an early NK cell response to HCV exposure. Only

a single healthcare worker developed high-level systemic infection and was studied up to week 17, when PegIFN/ribavirin therapy was initiated. Overall, NK/NKT cell responses appeared later (peak week 8) than in the subjects without detectable viremia (peak week 4), and NK cell degranulation and IFN-γ production were weaker. A limitation of our study is the absence of a negative control group of healthcare workers exposed to HCV-negative blood. However, click here one exposed healthcare worker without detectable viremia tested negative for cytokine, NKT, NK, and T-cell responses in all assays, which suggests that the needlestick injury was too small to transmit HCV. Conversely, the increase in T-cell responses to HCV, but not to Epstein-Barr virus (EBV) and human immunodeficiency virus (HIV) in the other healthcare workers, and the correlation between NK/NKT cell responses and T-cell responses supports the notion that the observed immune reactions were due to HCV exposure. While it is possible that innate and adaptive immune responses of the studied healthcare workers are each individually related to a third factor, such as the exposure type or the amount of antigen encountered, they may also support each other.