Journal Article

DKFZ-2018-01711

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png NK-cell responses are biased towards CD16-mediated effector functions in chronic Hepatitis B virus infection.

Schuch, A. ; Zecher, B. F. ; Müller, P. A. ; Correia, M. P.DKFZ* ; Daul, F. ; Rennert, C. ; Tauber, C. ; Schlitt, K. ; Boettler, T. ; Neumann-Haefelin, C. ; Hengel, H. ; Pircher, H. ; Cerwenka, A.DKFZ* ; Thimme, R. ; Hofmann, M.

2019
Wiley-Blackwell [S.l.]

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Please use a persistent id in citations: doi:10.1016/j.jhep.2018.10.006

Abstract: 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.

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Contributing Institute(s):

1. Nachwuchsgruppe Angeborene Immunität (D080)

Research Program(s):

1. 314 - Tumor immunology (POF3-314) (POF3-314)

Appears in the scientific report 2019

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Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 10 ; JCR ; NCBI Molecular Biology Database ; Nationallizenz ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection

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