Project Description

TP07: Dissecting NK cell-mediated immune responses against hepatitis B virus and hepatitis C virus infection

Natural Killer (NK) cells are cytotoxic and cytokine-producing innate immune cells that are highly enriched among lymphocytes in the liver and can mediate efficient antiviral immune responses. It is the aim of our project to dissect the mechanisms of the interaction of NK cells with HBV or HCV infected liver cells and the influence of the microenvironment in in vitro co-culture systems and with patient derived cells. Our studies should reveal novel knowledge of NK cell function/dysfunction in HBV and HCV infection that could potentially unravel novel targets for therapy.
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. 2018. NK-cell responses are biased towards CD16-mediated effector functions in chronic hepatitis B virus infection. J Hepatol. 70(3):351-360
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.
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
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 124:5305-16
Schlecker E, Fiegler N, Arnold A, Altevogt P, Rose-John S, Moldenhauer G, Sucker A, Paschen A, Textor S, Cerwenka A. 2014. Metalloprotease-mediated shedding of B7-H6, the ligand of the activating receptor NKp30, from tumor cells. Cancer Res 13:3429-40
Rölle A, Pollmann J, Cerwenka A. 2013. Memory of Infections - an Emerging Role for Natural Killer Cells. PLoS Pathogens 9:e1003548.
Fiegler N, Textor S, Arnold A, Rölle A, Oehme I, Breuhahn K, Moldenhauer G, Witzens-Harig M, Cer- wenka A. 2013. Downregulation of the activating NKp30 ligand B7-H6 by HDAC inhibitors impairs tumor cell recognition by NK cells. Blood 122:684-93
Ni J, Miller M, Stojanovic A, Garbi N, Cerwenka A. 2012. Sustained effector function of IL-12/15/18 pre- activated NK cells against established tumors. J Exp Med 209:2351-2365.
Textor S, Fiegler N, Arnold A, Porgador A, Hofmann TG, Cerwenka A. 2011. Human NK cells are alerted to induction of p53 in cancer cells by up-regulation of the NKG2D-ligands ULBP1 and ULBP2. Cancer Res 71:5998-6009.
Jarahian M, Fiedler M, Cohnen A, Djandji D, Hämmerling GJ, Gati C, Cerwenka A. 2011 Turner, PC., Moyer, RW., Watzl, C., Hengel, H., Momburg, F., Modulation of NKp30- and NKp46-Mediated Natural Killer Cell Responses by Poxviral Hemagglutinin, PLoS Pathogens 7:e1002195002195
Textor S, Dürst M, Janssen L, Accardi R, Tommasino M, Trunk MJ, Porgador A, Gissmann L, Cerwenka A.2008. Activating NK cell receptor ligands are differentially expressed during progression to cervical cancer. Int J Cancer 123:2343-53.
Cerwenka A, Lanier LL. 2001. NK cells, viruses and cancer. Nature Immunol Rev 1:41-49.
Cerwenka A, Bakker ABH, McClanahan T, Wagner J, Wu J, Phillips JH, Lanier LL. 2000. Retinoic acid early inducible genes define a ligand family for the activating NKG2D receptor in mice. Immunity 12: 721- 727.