Immunosurveillance of the Liver by Intravascular Effector CD8 + T Cells

Guidotti, Luca G.; Inverso, Donato; Sironi, Laura; Lucia, Pietro Di; Fioravanti, Jessica; Ganzer, Lucia; Fiocchi, Amleto; Vacca, Maurizio; Aiolfi, Roberto; Sammicheli, Stefano; Mainetti, Marta; Cataudella, Tiziana; Raimondi, Andrea; González‐Aseguinolaza, Gloria; Protzer, Ulrike; Ruggeri, Zaverio M.; Chisari, Francis V.; Isogawa, Masanori; Sitia, Giovanni; Iannacone, Matteo

doi:10.1016/j.cell.2015.03.005

Cited by 261 publications

(327 citation statements)

References 47 publications

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“…Current studies are in agreement with the hypothesis that the peculiar hemodynamic conditions of the liver microcirculation constitutively favor circulating platelets to form small and transient aggregates on the luminal surface of sinusoids; these aggregates appear to represent a preferential surface onto which circulating effector CD8 þ T cells arrest their course within the bloodstream (Guidotti et al 2015). In an ongoing effort to explain mechanistically why platelets are required to support the intrahepatic accumulation of virus-specific CD8 þ T cells, it was also found…”

Section: Models Of Disease Acute Hepatitissupporting

confidence: 85%

Mouse Models of Hepatitis B Virus Pathogenesis

Iannacone

Guidotti

2015

Cold Spring Harb Perspect Med

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The host range of hepatitis B virus (HBV) is limited to humans and chimpanzees. As discussed in the literature, numerous studies in humans and chimpanzees have generated a great deal of information on the mechanisms that cause viral clearance, viral persistence, and disease pathogenesis during acute or chronic HBV infection. Relevant pathogenetic studies have also been performed in those few species representing natural hosts of hepadnaviruses that are related to HBV, such as the woodchuck hepatitis virus and the duck hepatitis virus. Further insight has been gained from multidisciplinary studies in transgenic or humanized chimeric mouse models expressing and/or replicating HBV to varying degrees. We provide here a concise summary of the available HBV mouse models as well as of the contributions of these models to our understanding of HBV pathogenesis.H BV replicates noncytopathically in the hepatocyte and most of the clinical syndromes associated with HBV infection reflect the immune response, particularly the adaptive immune response (see below). Studies on HBV immunobiology have been hampered by the restricted host range of this virus and by the lack of readily infectable small animal models with a well-defined immune system. Over the last two decades, however, many questions pertaining to the immune-mediated mechanisms responsible for disease pathogenesis and viral clearance have been successfully addressed in mouse models. The various mouse models used and the most significant findings that have emerged from such models are the subject of this review.

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Section: Models Of Disease Acute Hepatitissupporting

confidence: 85%

Mouse Models of Hepatitis B Virus Pathogenesis

Iannacone

Guidotti

2015

Cold Spring Harb Perspect Med

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“…The development of in vivo imaging techniques, such as intravital microscopy (IVM) further allows to track cells in live animals over longer time periods in organs including cremaster muscle, liver, lung, brain and kidney (Figure 1C) (56,57), and have been greatly beneficial in analysing dynamic interaction between platelets and leukocytes (e.g. duration of interactions and behavioural changes in leukocytes and/or platelets upon contact) (10,53,55,58–61). …”

Section: Methods To Measure Plasmentioning

confidence: 99%

“…Similarly, platelet aggregates occur along hepatic sinusoids in necro-inflammatory foci in mice with acute viral hepatitis. This is substantial for recruitment of virus-specific CD8 + T cells causing hepatocellular injury (53,54) potentially via CD40L (100). …”

Section: Platelet-leukocyte Interactions In Pathologic Conditionsmentioning

confidence: 99%

Measuring and interpreting platelet-leukocyte aggregates

et al. 2018

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Platelets, besides their specialised role in haemostasis and atherothrombosis, actively modulate innate and adaptive immune responses with crucial roles in immune surveillance, inflammation and host defence during infection. An important prerequisite for platelet-mediated changes of immune functions involves direct engagement with different types of leukocytes. Indeed, increased platelet-leukocyte aggregates (PLAs) within the circulation and/or locally at the site of inflammation represent markers of many thrombo-inflammatory diseases, such as cardiovascular diseases, acute lung injury, renal and cerebral inflammation. Therefore, measurement of PLAs could provide an attractive and easily accessible prognostic and/or diagnostic tool for many diseases. To measure PLAs in different (patho-)physiological settings in human and animal models flow cytometric and microscopic approaches have been applied. These techniques represent complementary tools to study different aspects relating to the involvement of leukocyte subtypes and molecules, as well as location of PLAs within tissues, dynamics of their interactions and/or dynamic changes in leukocyte and platelet behaviour. This review summarises various approaches to measure and interpret PLAs and discusses potential experimental factors influencing platelet binding to leukocytes. Furthermore, we summarise insights gained from studies regarding the underlying mechanism of platelet-leukocyte interactions and discuss implications of these interactions in health and disease.

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“…Intrahepatic HBV-specific CD8 ? T cells are believed to be the key players in the non-cytopathic and cytopathic clearance of HBV [6,9].…”

Section: Innate Immunity In Hbv Infection: the Role Of Nk Cells And Dcsmentioning

confidence: 99%

Host–virus interactions in hepatitis B and hepatitis C infection

Yoshio

Kanto

2016

J Gastroenterol

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Hepatitis B virus (HBV) and hepatitis C virus (HCV) are among the most endemic pathogens worldwide, with more than 500 million people globally currently infected with these viruses. These pathogens can cause acute and chronic hepatitis that progress to liver cirrhosis or hepatocellular carcinoma. Both viruses utilize multifaceted strategies to evade the host surveillance system and fall below the immunological radar. HBV has developed specific strategies to evade recognition by the innate immune system and is acknowledged to be a stealth virus. However, extensive research has revealed that HBV is recognized by dendritic cells (DCs) and natural killer (NK) cells. Indoleamine-2, 3-dioxygenase is an enforcer of sequential immune reactions in acute hepatitis B, and this molecule has been shown to be induced by the interaction of HBV-infected hepatocytes, DCs, and NK cells. The interleukin-28B genotype has been reported to influence HCV eradication either therapeutically or spontaneously, but the biological function of its gene product, a type-III interferon (IFN-k3), remains to be elucidated. Human BDCA3 ? DCs have also been shown to be a potent producer of IFN-k3 in HCV infection, suggesting the possibility that BDCA3 ? DCs could play a key role in developing therapeutic HCV vaccine. Here we review the current state of research on immune responses against HBV and HCV infection, with a specific focus on innate immunity. A comprehensive study based on clinical samples is urgently needed to improve our understanding of the immune mechanisms associated with viral control and thus to develop novel immune modulatory therapies to cure chronic HBV and HCV infection.

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Immunosurveillance of the Liver by Intravascular Effector CD8 + T Cells

Cited by 261 publications

References 47 publications

Mouse Models of Hepatitis B Virus Pathogenesis

Mouse Models of Hepatitis B Virus Pathogenesis

Measuring and interpreting platelet-leukocyte aggregates

Host–virus interactions in hepatitis B and hepatitis C infection

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