Project Description

TP06: Role of platelets in control and clearance of hepatitis B virus infection via modulation of liver tissue environment and metabolism

The liver microenvironment containing different parenchymal and non-parenchymal liver cells and the hepatic metabolome play a pivotal role in the clearance of hepatic virus infections. Here we investigate the direct and indirect role of platelets in shaping the liver microenvironment, polarizing immune cell phenotypes and affecting liver metabolism in the context of viral infections. We analyse how platelets contribute to the reshaping of the liver immune niche, how they interact directly with hepatocytes in the context of antiviral therapies and how they affect clearance mechanisms. Our data might hint at novel targets used to support effective and long-lasting antiviral responses in the context of hepatic viral infections and reducing unwanted, immune-mediated side-effects.
A. Ramadori P, Klag T, Malek NP, Heikenwalder M. 2019. Platelets in chronic liver disease, from bench to bedside. Journal Hepatol Reports. DOI: 10.1016/j.jhepr.2019.10.001.
B. Namineni S, O‘Connor T*, Faure-Dupuy S*, Johansen P, …, Protzer U, Wohlleber D, Holzmann B, Bin-der M, … Lucifora J, Kalinke U, Knolle PA, Heikenwalder M. 2019. A dual role for hepatocyte-intrinsic canonical NF-κB signaling in virus control. J Hepatol. 01/12 in press.
C. Faure-Dupuy S, Delphin M, Aillot L, Dimier L, Lebossé F, Fresquet J, Parent R, Matter MS, Rivoire M, Bendriss-Vermare N, Salvetti A, Heide D, Flores L, Klumpp K, Lam A, Zoulim F, Heikenwalder M, Du-rantel D, Lucifora J. 2019. Hepatitis B virus-induced modulation of liver macrophage function promotes hepatocyte infection. J Hepatol. 23(19) 30422-2.
D. Malehmir M, Pfister D, Gallage S, Szydlowska M, Inverso D, Kotsiliti E, Leone V, Peiseler M, Surewaard BGJ, Rath D, Ali A, Wolf MJ, Drescher H, Healy ME, Dauch D, Kroy D, Krenkel O, Kohl-hepp M, Engleitner T, Olkus A, Sijmonsma T, Volz J, Deppermann C, Stegner D, Helbling P, Nombela-Arrieta C, Rafiei A, Hinterleitner M, Rall M, Baku F, Borst O, Wilson CL, Leslie J, O'Connor T, Weston CJ, Adams DH, Sheriff L, Teijeiro A, Prinz M, Bogeska R, Anstee N, Bongers MN, Notohamiprodjo M, Geisler T, Withers DJ, Ware J, Mann DA, Augustin HG, Vegiopoulos A, Milsom MD, Rose AJ, Lalor PF, Llovet JM, Pinyol R, Tacke F, Rad R, Matter M, Djouder N, Kubes P, Knolle PA, Unger K, Zender L, Nieswandt B, Gawaz M, Weber A, Heikenwalder M. 2019. Platelet GPIbα is a mediator and potential in-terventional target for NASH and subsequent liver cancer. Nat Med. 25(4):641-655.
E. Schneider A, Kurz S, Manske K, Janas M, Heikenwalder 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.
F. Baazim H, Schweiger M, Moschinger M, Xu H, Scherer T, Popa A, Gallage S, Ali A, Khamina K, Kosack L, Vilagos B, Smyth M, Lercher A, Friske J, Merkler D, Aderem A, Helbich TH, Heikenwalder M, Lang PA, Zechner R, Bergthaler A. 2019. CD8+ T cells induce cachexia during chronic viral infection. Nat Im-munol. 20(6):701-710.
G. Ringelhan M, Pfister D, O'Connor T, Pikarsky E, Heikenwalder M. 2018. The immunology of hepatocel-lular carcinoma. Nat Immunol. 19(3):222-232.
H. Xia Y, Stadler D, Lucifora J, Reisinger F, Webb D, Hösel M, Michler T, Wisskirchen K, Cheng X, Zhang K, Chou WM, Wettengel JM, Malo A, Bohne F, Hoffmann D, Eyer F, Thimme R, Falk CS, Thasler WE, Heikenwalder M, Protzer U. 2016. Interferon-γ and Tumor Necrosis Factor-α Produced by T Cells Re-duce the HBV Persistence Form, cccDNA, Without Cytolysis. Gastroenterology. 150(1):194-205.
I. Schölzel K, Schildberg FA, Börner C, Geiger S, Kurts C, Heikenwalder M, Knolle PA, Wohlleber D. 2014. Cross-allocation of MHC-class-I molecules among liver sinusoidal cells facilitates hepatic immune surveillance. J Heaptol. 61(3):600-8.
J. 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