Sustained Hyperresponsiveness of Dendritic Cells Is Associated with Spontaneous Resolution of Acute Hepatitis C

Pelletier, Sandy; Bédard, Nathalie; Said, Elias A.; Ancuța, Petronela; Bruneau, Julie; Shoukry, Naglaa H.

doi:10.1128/jvi.02445-12

Cited by 14 publications

(20 citation statements)

References 56 publications

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“…Subjects who mounted a successful immune response, resulting in spontaneous resolution of infection, had reduced numbers of mature pDCs and increased evidence of mDC activation, including increased cytokine production in response to a diverse array of TLR ligands, increased expression of the T cell costimulator CD86, and reduced expression of inhibitory ligands such as PD-L1 and PD-L2 (144). …”

Section: Innate Immune Cells In Chronic Hcv Infectionmentioning

confidence: 99%

Innate and Adaptive Immune Responses in Chronic HCV Infection

Dustin¹

2017

CDT

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Hepatitis C virus (HCV) remains a public health problem of global importance, even in the era of potent directly-acting antiviral drugs. In this chapter, I discuss immune response to acute and chronic HCV infection. The outcome of HCV infection is influenced by viral strategies that limit or delay the initiation of innate antiviral responses. This delay may enable HCV to establish widespread infection long before the host mounts effective T and B cell responses. HCV’s genetic agility, resulting from its high rate of replication and its error prone replication mechanism, enables it to evade immune recognition. Adaptive immune responses fail to keep up with changing viral epitopes. Neutralizing antibody epitopes may be hidden by decoy structures, glycans, and lipoproteins. T cell responses fail due to changing epitope sequences and due to exhaustion, a phenomenon that may have evolved to limit immune-mediated pathology. Despite these difficulties, innate and adaptive immune mechanisms do impact HCV replication. Immune-mediated clearance of infection is possible, occurring in 20–50% of people who contract the disease. New developments raise hopes for effective immunological interventions to prevent or treat HCV infection.

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Section: Innate Immune Cells In Chronic Hcv Infectionmentioning

confidence: 99%

Innate and Adaptive Immune Responses in Chronic HCV Infection

Dustin¹

2017

CDT

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“…Notably, these pathways have been investigated in vitro. In chronic hepatitis C, the number and function of pDCs have been found to be impaired [reviewed in [38,39]]. As type I IFN has been shown to negatively control pDC numbers in various in vitro infection models, it was thus suggested that type I IFN might negatively regulate pDC numbers during HCV infection.…”

Section: Induction Of Ifns and Isgs In Chronic Hcv Infection: The LIVmentioning

confidence: 99%

Activation of Type I and Type III Interferons in Chronic Hepatitis C

Mihm

2015

J Innate Immun

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Infection with hepatitis C virus (HCV) results in chronic and progressive liver disease. Persistency rates add up to 85%. Despite recognition of the virus by the human host in peripheral blood and in the liver, immune response appears to be ineffective in clearing infection. The ability to spontaneously eradicate the virus as well as the outcome of infection upon therapy with human recombinant interferon-α (IFN-α) was found to correlate most closely with genetic variations within the region encoding the IFN-λ genes, as revealed by genome-wide association studies on main ethnic populations in 2009. This review summarizes the induction of type I and type III IFN genes and their effectors, the IFN-stimulated genes. It focusses on the in vivo situation in chronic HCV infection in man both in the peripheral blood compartment and in the liver. It also addresses the impact of genetic polymorphisms in the region of type III IFN genes on their activation. Finally, it discusses how antiviral drugs (i.e. IFN-α, ribavirin and the direct-acting antivirals) may complementarily control the activation of endogenous IFNs and succeed in combatting infections.

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“…tuberculosis and Bordetella pertussis, as well as hepatitis C virus, have been reported to modulate DC maturation and cytokine expression and to support the generation of a regulatory milieu (27,38,41,42). Similarly, T. whipplei lysate was a weak activation stimulus only for M-DC and Mo-DC from control subjects in terms of the enhanced expression of costimulatory molecules and of IL-23.…”

Section: Discussionmentioning

confidence: 97%

“…This inability of Mo-DC to stimulate T. whipplei responses can be explained by the absence of a CD4 ϩ T cell memory for T. whipplei (4) but also could be due to an impaired functionality of Mo-DC. In fact, a significant decrease in expression of CD83 and PD-L1 of Mo-DC from CWD patients compared to control subjects upon maturation in the presence of T. whipplei lysate indicated impaired maturation as described for DC during, e.g., hepatitis C virus infection (38). More importantly, there seems to be an intrinsic dysfunction in the production of IL-12 by DC from CWD patients, since the proportion of IL-12-synthesizing M-DC was significantly reduced in CWD patients compared to that of controls.…”

Section: Discussionmentioning

confidence: 99%

Role of Dendritic Cells in the Pathogenesis of Whipple's Disease

et al. 2015

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c Accumulation of Tropheryma whipplei-stuffed macrophages in the duodenum, impaired T. whipplei-specific Th1 responses, and weak secretion of interleukin-12 (IL-12) are hallmarks of classical Whipple's disease (CWD). This study addresses dendritic cell (DC) functionality during CWD. We documented composition, distribution, and functionality of DC ex vivo or after in vitro maturation by fluorescence-activated cell sorting (FACS) and by immunohistochemistry in situ. A decrease in peripheral DC of untreated CWD patients compared to healthy donors was due to reduced CD11c high myeloid DC (M-DC). Decreased maturation markers CD83, CD86, and CCR7, as well as low IL-12 production in response to stimulation, disclosed an immature M-DC phenotype. In vitro-generated monocyte-derived DC from CWD patients showed normal maturation and T cell-stimulatory capacity under proinflammatory conditions but produced less IL-12 and failed to activate T. whipplei-specific Th1 cells. In duodenal and lymphoid tissues, T. whipplei was found within immature DC-SIGN ؉ DC. DC and proliferating lymphocytes were reduced in lymph nodes of CWD patients compared to levels in controls. Our results indicate that dysfunctional IL-12 production by DC provides suboptimal conditions for priming of T. whipplei-specific T cells during CWD and that immature DC carrying T. whipplei contribute to the dissemination of the bacterium.

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Sustained Hyperresponsiveness of Dendritic Cells Is Associated with Spontaneous Resolution of Acute Hepatitis C

Cited by 14 publications

References 56 publications

Innate and Adaptive Immune Responses in Chronic HCV Infection

Innate and Adaptive Immune Responses in Chronic HCV Infection

Activation of Type I and Type III Interferons in Chronic Hepatitis C

Role of Dendritic Cells in the Pathogenesis of Whipple's Disease

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