Project Description
Public­ations

TP13: Dynamics of antiviral T cell immunity against viral infection of the liver

Infections of the liver by hepatotropic viruses are controlled by the adaptive immune system. The dynamics of the antiviral CD8+ T cell immune response leading either to viral clearance or to persistent infection are incompletely defined. Using innovative imaging technologies, in vivo bioluminescence imaging and multispectral optoacoustic imaging, we will determine the dynamics of CD8+ T cell priming, migration and effector function during viral hepatitis. The results will identify key determinants for protective antiviral immunity against hepatotropic infections.
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. Outcome of anti-viral immunity in the liver is shaped by the level of antigen expressed in infected hepatocytes. Hepatology. 2018 May 5. doi: 10.1002/hep.30080. (Epub ahead of print)
Yuan D, Huang S, Berger E, Liu L, Gross N, Heinzmann F, Ringelhan M, Connor TO, Stadler M, Meister M, Weber J, Öllinger R, Simonavicius N, Reisinger F, Hartmann D, Meyer R, Reich M, Seehawer M, Leone V, Höchst B, Wohlleber D, Jörs S, Prinz M, Spalding D, Protzer U, Luedde T, Terracciano L, Matter M, Longerich T, Knolle P, Ried T, Keitel V, Geisler F, Unger K, Cinnamon E, Pikarsky E, Hüser N, Davis RJ, Tschaharganeh DF, Rad R, Weber A, Zender L, Haller D, Heikenwalder M. 2017. Kupffer Cell-Derived Tnf Triggers Cholangiocellular Tumorigenesis through JNK due to Chronic Mitochondrial Dysfunction and ROS. Cancer Cell. 31(6):771-789.e6. doi: 1016/j.ccell.2017.05.006.
Wohlleber D, Knolle PA. The role of liver sinusoidal cells in local hepatic immune surveillance. 2016. Clin Transl Immunology. 5(12):e117. doi: 10.1038/cti.2016.74. Review.
Taruttis A, Ntizachristos V. 2015. Advances in real-time multispectral optoacoustic imaging and its appli- cations. Nat Photonics 9:219-27.
Schölzel K, Schildberg FA, Welz M, Börner C, Geiger S, Kurts C, Heikenwalder M, Knolle PA, Wohlleber D. 2014. Transfer of MHC-class-I molecules among liver sinusoidal cells facilitates hepatic immune surveillance. J Hepatol 61:600-608
Böttcher JP, Schanz O, Wohlleber D, Abdullah Z, Debey-Pascher S, Staratschek-Jox A, Höchst B, Hegenbarth S, Grell J, Limmer A, Atreya I, Neurath MF, Busch DH, Schmitt E, van Endert P, Kolanus W, Kurts C, Schultze JL, Diehl L, Knolle PA. 2013. Liver-Primed Memory T Cells Generated under Noninflammatory Conditions Provide Anti-infectious Immunity. Cell reports 3: 779-795.
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: 574-583.
Stritzker J, Kirscher L, Scadeng M, Deliolanis NC, Morscher S, Symvoulidis P, Schaefer K, Zhang Q, Buckel L, Hess M, Donat U, Bradley WG, Ntziachristos V, Szalay AA. 2013. Vaccinia virus-mediated melanin production allows MR and optoacoustic deep tissue imaging and laser-induced thermotherapy of cancer. PNAS 110:3316-20.
Burton NC, Patel M, Morscher S, Driessen WH, Claussen J, Beziere N, Jetzfellner T, Taruttis A, Razan- sky D, Bednar B, Ntziachristos V. 2013. Multispectral opto-acoustic tomography (MSOT) of the brain and glioblastoma characterization. Neuroimage 65:522-8.
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 Activated through Cross-Presentation. Cell Reports 2: 478-487.
van Dam GM, Themelis G, Crane LM, Harlaar NJ, Pleijhuis RG, Kelder W, Sarantopoulos A, de Jong JS, Arts HJ, van der Zee AG, Bart J, Low PS, Ntziachristos V. 2011. Intraoperative tumor-specific fluorescence imaging in ovarian cancer by folate receptor-α targeting: first in-human results. Nat Med 17:1315-9.
Razansky D, Buehler A, Ntziachristos V. 2011. Volumetric real-time multispectral optoacoustic tomography of biomarkers. Nat Protoc 6:1121-9.
Stabenow D*, Frings M, Trück C, Gärtner K, Förster I, Kurts C, Tüting T, Odenthal M, Dienes HP, Cederbrant K, Protzer U, Knolle PA. 2010. Bioluminescence imaging allows measuring CD8+ T cell function in the liver. Hepatology 51: 1430-1437; *changed to Wohlleber after marriage.