Project Description

TP07: Dissecting NK cell reactivity against hepatitis B/D virus and in hepatitis C virus infection

The complexity of the innate immune response mediated by Natural Killer (NK) cells and other tissue-resident Innate Lymphoid Cell (ILC) subsets against different hepatitis viruses remains incompletely understood. Thus, in our project, we will study NK/ILC activation/dysfunction/exhaustion in response to HDV infection or HBV/HDV co-infection using in vitro co-culture systems and cells from hepatitis patients. Results of our study will not only facilitate the development of novel treatment options e.g. for HBV/HDV infection, but will also provide novel insight into general anti-viral mechanisms of NK cells and ILC subsets and their tissue specificity. We will further define the HCV responsive-specific NK subset and expand our previous study to different ILC subsets beyond NK cells not only from human peripheral blood, but also from human liver
Ni J, Wang X, Stojanovic A, Zhang Q, Wincher M, Bühler L, Arnold A, Correia MP, Winkler M, Koch PS, Sexl V, Höfer T, Cerwenka A. 2020. Single-Cell RNA Sequencing of Tumor-Infiltrating NK Cells Reveals that Inhibition of Transcription Factor HIF-1α Unleashes NK Cell Activity. Immunity. 2020 May 20:S1074-7613(20)30182-5. doi: 10.1016/j.immuni.2020.05.001. (TP07)
A. Schuch A, Zecher BF, Müller PA, Correia MP, Daul F, Rennert C, Tauber C, Schlitt K, Boettler T, Neumann-Haefelin C, Hengel H, Pircher H, Cerwenka A, Thimme R, Hofmann M. 2019. NK-cell responses are biased towards CD16-mediated effector functions in chronic Hepatitis B virus infection; J Hepatol. 70(3):351-360.
B. Pollmann J, Götz JJ, Rupp D, Strauss O, Granzin M, Grünvogel O, Mutz P, Kramer C, Lasitschka F, Lohmann V, Björkström NK, Thimme R, Bartenschlager R, Cerwenka A. 2018. Hepatitis C virus-induced natural killer cell proliferation involves monocyte-derived cells and the OX40/OX40L axis. J Hepatol. 68(3):421-430.
C. Pahl JHW, Koch J, Götz JJ, Arnold A, Reusch U, Gantke T, Rajkovic E, Treder M, Cerwenka A. 2018. CD16A Activation of NK Cells Promotes NK Cell Proliferation and Memory-Like Cytotoxicity against Cancer Cells. Cancer Immunol Res. 6(5):517-527.
D. Pollmann J, Rölle A, Hofmann M, Cerwenka A. 2017. Hepatitis C Virus and Human Cytomegalovirus-Natural Killer Cell Subsets in Persistent Viral Infections. Front Immunol. 8:566. Review.
E. Cerwenka A, Lanier LL. 2016. Natural killer cell memory in infection, inflammation and cancer. Nat Rev Immunol. 16(2):112-23. Review.
F. Rölle A, Halenius A, Ewen EM, Cerwenka A, Hengel H, Momburg F. 2016. CD2-CD58 interactions are pivotal for the activation and function of adaptive natural killer cells in human cytomegalovirus infection. Eur J Immunol. 46(10):2420-2425
G. Rölle A, Pollmann J, Ewen E, Halenius A, Hengel H, Cerwenka A. 2014. IL-12 producing monocytes and HLA-E drive NKG2C+ NK cell expansion in HCMV infection. J Clin Invest 124(12):5305-16
H. Stojanovic A, Fiegler N, Brunner-Weinzierl M, Cerwenka A. 2014. CTLA-4 is expressed by activated mouse NK cells and inhibits NK Cell IFN-γ production in response to mature dendritic cells. J Immunol. 192(9):4184-91
I. Rölle A, Pollmann J, Cerwenka A. 2013. Memory of Infections - an Emerging Role for Natural Killer Cells. PLoS Pathogens 9:e1003548.
J. Ni J, Miller M, Stojanovic A, Garbi N, Cerwenka A. 2012. Sustained effector function of IL- 12/15/18 preactivated NK cells against established tumors. J Exp Med 209(13):2351-2365.