Abstract
Natural killer (NK) cells are abundant in the liver and have been implicated in inducing hepatocellular damage in patients with chronic hepatitis B virus (HBV) infection. However, the role of NK cells in acute HBV infection remains to be elucidated. We comprehensively characterized NK cells and investigated their roles in HBV clearance and liver pathology in 19 chronic hepatitis B (CHB) patients and 21 acute hepatitis B (AHB) patients as well as 16 healthy subjects. It was found that NKp46+ NK cells were enriched in the livers of AHB and CHB patients. We further found that peripheral NK cells from AHB patients expressed higher levels of activation receptors and lower levels of inhibitory receptors than those from CHB patients and HC subjects, thus displaying the increased cytolytic activity and interferon-γ production. NK cell activation levels were also correlated positively with serum alanine aminotransferase levels and negatively with plasma HBV DNA levels in AHB patients, which is further confirmed by the longitudinal follow-up of AHB patients. Serum pro-inflammatory cytokine and chemokine levels were also increased in AHB patients as compared with CHB and HC subjects. Thus, the concomitantly increased interferon-γ and cytotoxicity of NK cells were associated with liver injury and viral clearance in AHB patients.
Highlights
Hepatitis B virus (HBV) infection is a major human threat that affects approximately 400 million people worldwide
It was observed that CD32CD56bright Natural killer (NK) cells were significantly expanded in both chronic hepatitis B (CHB) and acute hepatitis B (AHB) patients compared to the HC group
CD32CD56dim NK cells were greatly reduced in CHB and AHB patients compared with the HC group (Figure 1B)
Summary
Hepatitis B virus (HBV) infection is a major human threat that affects approximately 400 million people worldwide. While HBV infection in utero or early in life results in chronic infection, adults infected with this virus usually develop an acute self-limited infection [1]. During acute HBV infection, virus-specific T cell responses are often readily detectable and multi-specific [5,6,7]; while in chronic HBV infections, virus-specific T cell responses are generally weak and display functional exhaustion as a result of the upregulation of programmed death-1 [8,9], T cell attrition through Bcl signaling [10] and impaired T cell receptor signaling through the f-chain [11]. Despite the associations between the adaptive T cell responses, viral clearance and liver damage during acute and chronic HBV infection, the innate immune effector mechanisms that are responsible for viral clearance and liver pathogenesis remained obscure [12]
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