Obiettivo
Hepatitis B virus (HBV) and hepatitis C virus (HCV) infect the liver, and are unique in their capacity to cause persistent infection, cirrhosis, and liver cancer. The lack of experimental approaches to study these infections, due to the limited host range to humans and chimpanzees, have hampered the understanding of fundamental issues regarding their pathogenesis. It is now clear that both infections are very similar, HBV and HCV are non-cytopathic viruses that replicate exclusively in the hepatocytes, thus most of the clinical syndromes are associated to a virus-specific CD8 T cell-mediated immunopathology that fails to clear HBV or HCV infection, creating a chronic necroinflammatory process which results in hepatic fibrosis/cirrhosis and hepatocellular carcinoma (HCC). While some of the rules governing CD8 T cell behavior in the liver have been characterized at the population level, we have only limited knowledge of the precise dynamics of intrahepatic CD8 T cell migration and interaction with other cell types at the single-cell level. For instance,it has been previously shown that the intrahepatic recruitment of virus- specific CTLs is platelet-dependent, and in vitro experiments suggest that specific effector CD8 T cells tightly interact with activated platelets. Advances in the field of live imaging allow us for the first time to answer these questions directly in the living animal, by visualizing liver immunopathology as it progresses in vivo. To this end, the recently developed intravital microscopy (IVM) model in the liver of anesthetized mice, allows to generate time-lapse movies to dissect the interactive behavior of intrahepatic CD8 T cells,to elucidate the cellular and molecular mechanisms by which effector CD8 T cells migrate to the liver,recognizing hepatic antigens in vivo within the normal or fibrotic liver, and how this affects the T-cell mediated immunopathology that finally leads to fibrosis and hepatocellular carcinoma.
Campo scientifico
- medical and health sciencesclinical medicineoncologyliver cancer
- natural sciencesbiological sciencesmicrobiologyvirology
- medical and health scienceshealth sciencesinfectious diseasesDNA viruseshepatitis B
- medical and health scienceshealth sciencesinfectious diseasesRNA viruseshepatitis C
- medical and health sciencesclinical medicinehepatology
Argomento(i)
Invito a presentare proposte
FP7-PEOPLE-2012-IEF
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Meccanismo di finanziamento
MC-IEF - Intra-European Fellowships (IEF)Coordinatore
20132 Milano
Italia