Natural killer cells contribute to hepatic injury and help in viral persistence during progression of hepatitis B e-antigen-negative chronic hepatitis B virus infection. (August 2016)

• Record Type: Journal Article
• Authors: Ghosh, S.; Nandi, M.; Pal, S.; Mukhopadhyay, D.; Chakraborty, B.C.; Khatun, M.; Bhowmick, D.; Mondal, R.K.; Das, S.; Das, K.; Ghosh, R.; Banerjee, S.; Santra, A.; Chatterjee, M.; Chowdhury, A.; Datta, S.
• Is Part Of: Clinical microbiology and infection. Volume 22:Number 8(2016)
• Page Start: 733.e9
• Page End: 733.e19
• Publication Date: 2016-08
• Subjects: CD4+ T-cell depletion -- Hepatitis B e-antigen-negative chronic Hepatitis B virus infection -- Natural killer cells -- Natural killer receptor ligands -- Perforin -- Reduced interferon-γ -- TRAIL; Medical microbiology -- Periodicals; Diagnostic microbiology -- Periodicals; Communicable diseases -- Periodicals; Infection -- Periodicals; 616.01
• DOI: 10.1016/j.cmi.2016.05.009
• Languages: English
• ISSNs: 1198-743X

Abstract

Abstract: Hepatitis B e-antigen negative (e(−)) chronic HBV infection (CHI) encompasses a heterogeneous clinical spectrum ranging from inactive carrier (IC) state to e(−) chronic hepatitis B (CHB), cirrhosis and hepatic decompensation. In the backdrop of dysfunctional virus-specific T cells, natural killer (NK) cells are emerging as innate effectors in CHI. We characterized CD3 − CD56 + NK cells in clinically well-defined, treatment-naive e(−) patients in IC, e(−)CHB or decompensated liver cirrhosis (LC) phase to appraise their role in disease progression. The NK cell frequencies increased progressively with disease severity (IC 8.2%, e(−)CHB 13.2% and LC 14.4%). Higher proportion of NK cells from LC/e(−)CHB expressed CD69, NKp46, NKp44, TRAIL and perforin, the last two being prominent features of CD56 bright and CD56 dim NK subsets, respectively. The frequencies of CD3 − CD56 + NK cells together with TRAIL + CD56 bright and Perforin + CD56 dim NK cells correlated positively with serum alanine transaminase levels in e(−)CHB/LC. K562 cell-stimulated NK cells from e(−)CHB/LC exhibited significantly greater degranulation but diminished interferon-γ production than IC. Further, Perforin + NK cell frequency inversely correlated with autologous CD4 + T-cell count in e(−) patients and ligands of NK receptors were over-expressed in CD4 + T cells from e(−)CHB/LC relative to IC. Co-culture of sorted CD56 dim NK cells and CD4 + T cells from e(−)CHB showed enhanced CD4 + T-cell apoptosis, which was reduced by perforin inhibitor, concanamycin A, suggesting a possible perforin-dependent NK cell-mediated CD4 + T-cell depletion. Moreover, greater incidence of perforin-expressing NK cells and decline in CD4 + T cells were noticed intrahepatically in e(−)CHB than IC. Collectively, NK cells contribute to the progression of e(−)CHI by enhanced TRAIL- and perforin-dependent cytolytic activity and by restraining anti-viral immunity through reduced interferon-γ secretion and perforin-mediated CD4 + T-cell lysis.