TY  - JOUR
AU  - Schuch, Anita
AU  - Zecher, Britta Franziska
AU  - Müller, Philipp Andreas
AU  - Correia, Margareta P
AU  - Daul, Franziska
AU  - Rennert, Charlotte
AU  - Tauber, Catrin
AU  - Schlitt, Karolin
AU  - Boettler, Tobias
AU  - Neumann-Haefelin, Christoph
AU  - Hengel, Hartmut
AU  - Pircher, Hanspeter
AU  - Cerwenka, Adelheid
AU  - Thimme, Robert
AU  - Hofmann, Maike
TI  - NK-cell responses are biased towards CD16-mediated effector functions in chronic Hepatitis B virus infection.
JO  - Journal of hepatology
VL  - 70
IS  - 3
SN  - 0168-8278
CY  - [S.l.]
PB  - Wiley-Blackwell
M1  - DKFZ-2018-01711
SP  - 351-360
PY  - 2019
AB  - Phenotypical 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:30342116
DO  - DOI:10.1016/j.jhep.2018.10.006
UR  - https://inrepo02.dkfz.de/record/141188
ER  -