Natural killer cells (NK) are one of the key players in the eradication and control of viral infections. Infections with the hepatitis B virus (HBV) may lead to persistence in a subgroup of patients, and impaired NK cell functions have been observed in these patients. Crosstalk with other immune cells has been shown to modulate the function of NK cells. We studied the functional crosstalk between NK cells and plasmacytoid dendritic cell (pDC) and its modulation by HBV. Healthy human peripheral blood-derived NK cells and pDC were purified and cocultured in the presence or absence of HepG2.2.15-derived HBV under various in vitro conditions. The functionality of NK cells was assessed by evaluation of activation markers, cytokine production and cytotoxicity of carboxyfluorescein succinimidyl ester-labelled K562 target cells by flow cytometry or immunoassays. Additionally, the crosstalk was examined using NK and pDC from patients with chronic HBV. The activation of NK cells in cocultures with pDC, as demonstrated by CD69, CD25 and HLA-DR, was not affected by the presence of HBV. Similarly, when cocultured with pDC, the cytotoxic potential of NK cells was not influenced by HBV. However, HBV significantly inhibited pDC-induced IFN-γ production by NK cells both in the presence and in the absence of CpG. As HBV did not affect cytokine-induced IFN-γ production by NK cells cultured alone, the suppressive effect of HBV on NK cell function was mediated via interference with pDC-NK cell interaction. In contrast to other viruses, HBV does not activate pDC-NK cell interaction but inhibits pDC-induced NK cell function. In parallel with NK cells of patients with chronic HBV, which show diminished cytokine production with normal cytotoxicity, HBV specifically suppressed pDC-induced IFN-γ production by NK cells without affecting their cytolytic ability. These data demonstrate that HBV modulates pDC-NK cell crosstalk, which may contribute to HBV persistence.

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Keywords cell interaction, hepatitis B virus, interferon -γ, natural killer cell, plasmacytoid dendritic cell
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Journal Journal of Viral Hepatitis
Shi, C.C, Tjwa, E.T.T.L, Biesta, P.J, Boonstra, P.A, Xie, Q, Janssen, H.L.A, & Woltman, A.M. (2012). Hepatitis B virus suppresses the functional interaction between natural killer cells and plasmacytoid dendritic cells. Journal of Viral Hepatitis, 19(2). doi:10.1111/j.1365-2893.2011.01496.x