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primary topic: Cooperation of innate immune cells during Hepatitis C virus infection

Cooperation of innate immune cells during Hepatitis C virus infection
type: Article
abstract: Induction of an innate immune response requires recognition of pathogen associated molecular patterns (PAMPs) by pattern recognition receptors (PRRs). However, pathogens like the Hepatitis C virus (HCV) have evolved mechanisms to evade innate immune responses in infected host cells. HCV specifically infects hepatocytes, thus specialized immune cells are not affected by the immune modulatory mechanisms exerted by HCV. Indeed, it was observed that plasmacytoid dendritic cells (pDCs) recognize HCV infected cells and respond with IFNα secretion. In this study the response of innate immune cells against HCV was further analyzed in a co-culture of HCV subgenomic replicon (SGR) cells and peripheral blood mononuclear cells (PBMCs). It was confirmed that IFNα is produced by pDCs in this co-culture and it was shown that the secreted IFNα inhibits viral replication. Subsequently, it was demonstrated that pDC activation is triggered by viral RNA and that recognition of viral RNA in pDCs is dependent on TLR7. The transfer of viral RNA from infected cells into pDCs required cell-cell contacts. Following the characterization of the pDC response, a Luminex assay was performed to detect further cytokines and chemokines secreted by PBMCs in response to HCV SGR cells. As secretion of IFNγ was detected, NK cells were assumed to be activated. NK cell depletion from PBMCs resulted in loss of IFNγ, proving that NK cells are the source of IFNγ. Moreover, it was observed that also monocytes play a role in the anti-viral response. Flow cytometry and ImageStream analysis revealed an uptake of particles from HCV SGR cells by monocytes. The particles were found to be apoptotic vesicles, as PBMCs induced apoptosis in HCV SGR cells via tumor necrosis factor-related apoptosis inducing ligand (TRAIL) expression on NK cells. However, interactions between pDCs, NK cells and monocytes were required for efficient clearance of HCV SGR cells, as purified immune cells alone did not kill HCV SGR cells. Alt…
date: 2017
author list: authors
type: EPrint
type: DoctoralThesisEPrint
is part of: repository
has document: Cooperation of innate immune cells during Hepatitis C virus infection (PDF)
has document: Cooperation of innate immune cells during Hepatitis C virus infection (Other)
subject: 570 Biowissenschaften, Biologie

Cooperation of innate immune cells during Hepatitis C virus infection (PDF)
type: Document
has file: PhD Thesis Volker Klöss.pdf
has part: PhD Thesis Volker Klöss.pdf

Volker Klöss
type: Person
given name: Volker
family name: Klöss

Cooperation of innate immune cells during Hepatitis C virus infection (Other)
type: Document
is version of: Cooperation of innate immune cells during Hepatitis C virus infection (PDF)
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Cooperation of innate immune cells during Hepatitis C virus infection (Other)
type: Document
is version of: Cooperation of innate immune cells during Hepatitis C virus infection (PDF)
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Cooperation of innate immune cells during Hepatitis C virus infection (Other)
type: Document
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Cooperation of innate immune cells during Hepatitis C virus infection (Other)
type: Document
is version of: Cooperation of innate immune cells during Hepatitis C virus infection (PDF)
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Cooperation of innate immune cells during Hepatitis C virus infection (Other)
type: Document
is version of: Cooperation of innate immune cells during Hepatitis C virus infection (PDF)
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HTML Summary of #23211 Cooperation of innate immune cells during Hepatitis C virus infection
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primary topic: Cooperation of innate immune cells during Hepatitis C virus infection

570 Biowissenschaften, Biologie
type: Concept
preferred label: 570 Life sciences @en