Project Description
Public­ations

TP13: Dynamics of antiviral immunity against hepatitis B virus in the liver

We investigate the impact of antigen levels, circulating antigen as well as presented antigens on the single cell level, on the dynamics of T cell immunity and the outcome of HBV infection. Using sophisticated HBV-infection models in genetically well-defined mice in combination with bioluminescence imaging and multispectral flow cytometry/multiparametric immunohistology, we aim to unravel the decisive factors leading to acute or chronic infection. We will also focus on metabolic, phenotypical and functional differences between virus-specific CD8 T cells in mice with either acute or chronic infection.
A. Alfei F, Kanev K, Hofmann M, Wu M, Ghoneim HE, Roelli P, Utzschneider DT, von Hoesslin M, Cullen JG, Fan Y, Eisenberg V, Wohlleber D, Steiger K, Merkler D, Delorenzi M, Knolle PA, Cohen CJ, Thim-me R*, Youngblood B*, Zehn D*. 2019. TOX reinforces the phenotype and longevity of exhausted T cells in chronic viral infection. Nature. 571(7764):265-269. * co-corresponding authors
B. Schneider A, Kurz S, Manske K, Janas M, Heikenwälder M, Misgeld T, Aichler M, Weissmann SF, Zischka H, Knolle PA, Wohlleber D. 2019. Single organelle analysis to characterize mitochondrial func-tion and crosstalk during viral infection. Sci Rep. 9(1):8492
C. Welz M, Eickhoff S, Abdullah Z, Trebicka J, Gartlan KH, Spicer JA, Demetris AJ, Akhlaghi H, Anton M, Manske K, Zehn D, Nieswandt B, Kurts C, Trapani JA, Knolle P*, Wohlleber D*, Kastenmüller W*. 2018. Perforin inhibition protects from lethal endothelial damage during fulminant viral hepatitis. Nat Comm. 9(1):4805. * equal contribution
D. Manske K, Kallin N, König V, Schneider A, Kurz S, Bosch M, Welz M, Cheng RL, Bengsch B, Steiger K, Protzer U, Thimme R, Knolle PA, Wohlleber D. 2018. Outcome of Antiviral Immunity in the Liver is Shaped by the Level of Antigen Expressed in Infected Hepatocytes. Hepatology. 68(6):2089-2105
E. Schölzel K, Schildberg FA, Börner C, Geiger S, Kurts C, Heikenwälder M, Knolle PA, Wohlleber D. 2014. Cross-allocation of MHC-class-I molecules among liver sinusoidal cells facilitates hepatic immune surveillance. J Hepatol. 61(3):600-8.
F. Wolf MJ, Adili A, Piotrowitz K, Abdullah Z, Boege Y, Stemmer K, Ringelhan M, Simonavicius N, Egger M, Wohlleber D, Lorentzen A, Einer C, Schulz S, Clavel T, Protzer U, Thiele C, Zischka H, Moch H, Tschöp M, Tumanov AV, Haller D, Unger K, Karin M, Kopf M, Knolle P, Weber A, Heikenwalder M. 2014. Metabolic activation of intrahepatic CD8+ T cells and NKT cells causes nonalcoholic steatohepa-titis and liver cancer via cross-talk with hepatocytes. Cancer Cell. 26(4):549-64.
G. Huang LR, Wohlleber D, Reisinger F, Jenne CN, Cheng RL, Abdullah Z, Schildberg FA, Odenthal M, Dienes HP, van Rooijen N, Schmitt E, Garbi N, Croft M, Kurts C, Kubes P, Protzer U, Heikenwalder M, Knolle PA. 2013. Intrahepatic myeloid-cell aggregates enable local proliferation of CD8+ T cells and successful immunotherapy against chronic viral liver infection. Nat Immunol. 14(6):574-83.
H. Wohlleber D, Kashkar H, Gärtner K, Frings MK, Odenthal M, Hegenbarth S, Börner C, Arnold B, Hämmerling G, Nieswandt B, van Rooijen N, Limmer A, Cederbrant K, Heikenwalder M, Pasparakis M, Protzer U, Dienes HP, Kurts C, Krönke M, Knolle PA. 2012. TNF-induced target cell killing by CTL acti-vated through cross-presentation. Cell Rep. 2(3):478-87.
I. Hösel M, Broxtermann M, Janicki H, Esser K, Arzberger S, Hartmann P, Gillen S, Kleef J, Stabenow D, Odenthal M, Knolle P, Hallek M, Protzer U, Büning H. 2012. Toll-like receptor 2-mediated innate immune response in human nonparenchymal liver cells toward adeno-associated viral vectors. Hepatology. 55(1):287-97.
J. Stabenow D, Frings M, Trück C, Gärtner K, Förster I, Kurts C, Tüting T, Odenthal M, Dienes HP, Ceder-brant K, Protzer U, Knolle PA. 2010. Bioluminescence imaging allows measuring CD8 T cell function in the liver. Hepatology 51: 1430-1437.