Work from our laboratory is aimed at defining the molecular and cellular bases for liver disease in the pathogenesis of hepatitis B virus (HBV) and other hepatotropic infections. Using HBV transgenic mice and mice infected with adenovirus or lymphocytic choriomeningitis virus (LCMV), we showed that many antigen non-specific inflammatory cells are recruited into the liver by cytotoxic T cells (CTLs) and this process significantly amplifies the severity of liver disease. Recent studies have shown that neutrophils play an important pathogenetic role in our models. Indeed, neutrophils rapidly enter the inflamed organ and recruit most antigen non-specific mononuclear cells via the production of metalloproteinases (i.e. MMP-8 and MMP-9) that facilitate leukocyte trafficking by remodeling of the extracellular matrix. Furthermore, recent results indicated a significant contribution of platelets in the pathogenetic mechanism of CTL-induced liver disease. Platelets accumulate within necroinflammatory foci of the liver and their depletion reduced the intrahepatic number of virus-specific CTLs and significantly ameliorated the severity of liver damage. Since the inhibition of CTL-mediated liver injury can occur under conditions where CTL priming is not involved, it is likely that depletion of platelets impaired the capacity of virus-specific CTLs to migrate into the liver, recognize antigen and/or perform effector functions. In addition, platelets may contribute to immunopathology by directly inducing tissue damage and experiments aimed at defining a direct cytopathic role for platelets are currently underway in our laboratory.
M.D., Medical School, University of Milan, Italy, 1989
Ph.D., Pathology, University of Parma, Medical School, Parma, Italy, 1994
Iannacone, M. & Guidotti, L. G. Mouse models of hepatitis B virus pathogenesis. (2015). Cold Spring Harbor Perspectives in Medicine, 5. PMCID: PMC4632861.
Guidotti, L. G. & Lannacone, M. Editorial overview: Viral pathogenesis. (2015). Current Opinion in Virology, 11, v.
Sitia, G., Iannacone, M. & Guidotti, L. G. Anti-platelet therapy in the prevention of hepatitis B virus-associated hepatocellular carcinoma. (2013). Journal of Hepatology, 59(5), 1135-1138.
Tonti, E., de Oya, N. J., Galliverti, G., Moseman, E. A., Di Lucia, P., Amabile, A., Sammicheli, S., De Giovanni, M., Sironi, L., Chevrier, N., Sitia, G., Gennari, L., et al. Bisphosphonates target B cells to enhance humoral immune responses. (2013). Cell Reports, 5(2), 323-330. PMCID: PMC3838640.
Guidotti, L. G. & Iannacone, M. Effector CD8 T cell trafficking within the liver. (2013). Molecular Immunology, 55(1), 94-99. PMCID: PMC3578146.
Castagnaro, L., Lenti, E., Maruzzelli, S., Spinardi, L., Migliori, E., Farinello, D., Sitia, G., Harrelson, Z., Evans, S. M., Guidotti, L. G., Harvey, R. P., Brendolan, A. Nkx2-5(+)islet1(+) mesenchymal precursors generate distinct spleen stromal cell subsets and participate in restoring stromal network integrity. (2013). Immunity, 38(4), 782-791. PMCID: PMC3652017.
Patel, A. S., Smith, A., Nucera, S., Biziato, D., Saha, P., Attia, R. Q., Humphries, J., Mattock, K., Grover, S. P., Lyons, O. T., Guidotti, L. G., Siow, R., et al. TIE2-expressing monocytes/macrophages regulate revascularization of the ischemic limb. (2013). EMBO Molecular Medicine, 5(6), 858-869. PMCID: PMC3779448.
Sitia, G., Aiolfi, R., Di Lucia, P., Mainetti, M., Fiocchi, A., Mingozzi, F., Esposito, A., Ruggeri, Z. M., Chisari, F. V., Iannacone, M. & Guidotti, L. G. Antiplatelet therapy prevents hepatocellular carcinoma and improves survival in a mouse model of chronic hepatitis B. (2012). Proceedings of the National Academy of Sciences of the United States of America, 109(32), E2165-E2172. PMCID: PMC3420192.
Tonti, E., Fedeli, M., Napolitano, A., Iannacone, M., von Andrian, U. H., Guidotti, L. G., Abrignani, S., Casorati, G. & Dellabona, P. Follicular helper nkt cells induce limited b cell responses and germinal center formation in the absence of cd4(+) t cell help. (2012). Journal of Immunology, 188(7), 3217-3222. PMCID: PMC3559029.
Sitia, G., Iannacone, M., Aiolfi, R., Isogawa, M., van Rooijen, N., Scozzesi, C., Bianchi, M. E., von Andrian, U. H., Chisari, F. V. & Guidotti, L. G. Kupffer cells hasten resolution of liver immunopathology in mouse models of viral hepatitis. (2011). PLoS Pathogens, 7, e1002061. PMCID: PMC3107209.