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000141188 1001_ $$aSchuch, Anita$$b0
000141188 245__ $$aNK-cell responses are biased towards CD16-mediated effector functions in chronic Hepatitis B virus infection.
000141188 260__ $$a[S.l.]$$bWiley-Blackwell$$c2019
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000141188 520__ $$aPhenotypical and functional NK-cell alterations are well described in chronic Hepatitis B virus (cHBV) infection. However, it is largely unknown whether these alterations result from general effects on the overall NK-cell population or the emergence of distinct NK-cell subsets. Indeed, memory-like NK cells emerge in association with human cytomegalovirus (HCMV) infection that is common in cHBV infection. These memory-like NK cells display an altered phenotype and functionality including superior CD16-mediated effector functions.To assess the impact of memory-like NK cells on phenotypic and functional alterations in cHBV infection we performed in-depth analyses of circulating NK cells in 52 cHBV patients, 45 chronically HCV-infected patients and 50 healthy donors (HD) with respect to their HCMV serostatus.In cHBV/HCMV+ patients, FcεRIγ- memory-like NK cells were present in higher frequencies and with higher prevalence compared to HD/HCMV+. This pronounced HCMV-associated memory-like NK-cell expansion could be identified as key determinant of the NK-cell response in cHBV infection. Furthermore, we observed that memory-like NK cells consist of epigenetically distinct subsets and exhibit metabolic key characteristics of long-living cells. Despite ongoing chronic infection, the phenotype of memory-like NK cells was conserved in cHBV/HCMV+ patients. Functional characteristics of memory-like NK cells also remained largely unaffected by cHBV infection with the exception of an increased degranulation capacity in response to CD16 stimulation that was, however, detectable in both, memory-like and conventional NK cells.The emergence of HCMV-associated memory-like NK cells shapes the overall NK-cell response in cHBV infection and contributes to a general shift towards CD16-mediated effector functions. HCMV coinfection therefore needs to be considered with respect to the design of immunotherapeutic approaches in HBV cure targeting NK cells.In chronic hepatitis B virus infection, the NK-cell phenotype and function is altered in comparison to healthy donors. In this study, we demonstrate that this is linked to the emergence of a distinct NK-cell subset, namely memory-like NK cells. The emergence of these memory-like NK cells is associated with co-infection of human cytomegalovirus that affects the majority of patients with chronic hepatitis B.
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000141188 7001_ $$aZecher, Britta Franziska$$b1
000141188 7001_ $$aMüller, Philipp Andreas$$b2
000141188 7001_ $$0P:(DE-HGF)0$$aCorreia, Margareta P$$b3
000141188 7001_ $$aDaul, Franziska$$b4
000141188 7001_ $$aRennert, Charlotte$$b5
000141188 7001_ $$aTauber, Catrin$$b6
000141188 7001_ $$aSchlitt, Karolin$$b7
000141188 7001_ $$aBoettler, Tobias$$b8
000141188 7001_ $$aNeumann-Haefelin, Christoph$$b9
000141188 7001_ $$aHengel, Hartmut$$b10
000141188 7001_ $$aPircher, Hanspeter$$b11
000141188 7001_ $$0P:(DE-He78)d2b4dd8bdffe4aaa0f5e30e91587766f$$aCerwenka, Adelheid$$b12$$udkfz
000141188 7001_ $$aThimme, Robert$$b13
000141188 7001_ $$aHofmann, Maike$$b14
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