Comparable functions of plasmacytoid and monocyte-derived dendritic cells in chronic hepatitis C patients and healthy donors

Piccioli, Diego; Tavarini, Silvia; Nuti, Sandra; Colombatto, P.; Brunetto, Maurizia Rossana; Bonino, Ferruccio; Ciccorossi, P.; Zorat, Francesca; Pozzato, Gabriele; Comar, Consuelo; Abrignani, Sergio; Wack, Andreas

doi:10.1016/j.jhep.2004.09.014

Cited by 98 publications

(87 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In addition, reduced frequencies and impaired capacity of peripheral blood DCs in both acute and chronic HCV infection have been seen [54; 55]. However, not all studies have seen differences either in frequency [56] or function of pDC [57]. In some studies, pDC and mDC are be reduced in number but appear to be functional once differences in cell number are corrected for [58; 59].…”

Section: Natural Killer (Nk) and Nkt Cellmentioning

confidence: 99%

Immune responses during acute and chronic infection with hepatitis C virus

Ishii

Koziel

2008

Clinical Immunology

View full text Add to dashboard Cite

Hepatitis C virus (HCV) induces persistent infection and causes chronic liver disease in most infected patients. Vigorous HCV-specific CD4+ and CD8+ T cell responses against HCV multiple epitopes are necessary for spontaneous viral clearance during the acute phase, but the virus appears to have multiple strategies to evade these defenses. There are relatively few studies on the role of immune responses during the chronic phase of infection. CD4+ T cell responses appear to protect against liver injury and may be important to clearance during interferon and ribavirin based therapy. Classic cytotoxic T cells (CTL) may primarily damage the liver in chronic HCV, but there may be subpopulations of T cells that protect against liver inflammation. Resolution of these outstanding questions is important to the development of a prophylactic vaccine as well as improving therapeutic options for those with chronic infection.

show abstract

Section: Natural Killer (Nk) and Nkt Cellmentioning

confidence: 99%

Immune responses during acute and chronic infection with hepatitis C virus

Ishii

Koziel

2008

Clinical Immunology

View full text Add to dashboard Cite

show abstract

“…HCV structural and nonstructural proteins have also been reported to inhibit DC maturation and function (16,46). In contrast, other studies have identified no defect in MoDC IL-12 production or T-cell stimulatory function (38,39,42). Similarly, differing results have been reported on pDC function in chronic HCV infection, with some studies finding decreased pDC frequency, IFN-␣ production, and T-cell stimulatory capacity, while others have found no defects (2,38,39,42,49,51,54).…”

mentioning

confidence: 92%

Differential Effects of Hepatitis C Virus JFH1 on Human Myeloid and Plasmacytoid Dendritic Cells

Liang¹,

Russell

Yonkers³

et al. 2009

J Virol

View full text Add to dashboard Cite

Dendritic cells (DCs) are reported to be functionally deficient during chronic hepatitis C virus (HCV) infection.Differing results have been reported on direct effects of intact replicative-form HCV on DC function. To better understand the effect of HCV on DC function, we treated freshly purified human myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) with HCV JFH1. We found that HCV upregulated mDC maturation marker (CD83, CD86, and CD40) expression and did not inhibit Toll-like receptor 3 (TLR3) ligand [poly(I:C)]-induced mDC maturation, a finding consistent with the phenotype of DCs from HCV-infected subjects. At the same time, HCV JFH1 inhibited the ability of poly(I:C)-treated mDCs to activate naive CD4 T cells. In contrast, although there was no direct effect of virus on pDC maturation, HCV JFH1 inhibited TLR7 ligand (R848)-induced pDC CD40 expression, and this was associated with impaired ability to activate naive CD4 T cells. Parallel experiments with recombinant HCV proteins indicated HCV core protein may be responsible for a portion of the activity. Furthermore, HCV-mediated mDC maturation was dependent upon CD81-E2 interaction and, in part, TLR2. Using UV-treated HCV, we show that HCV-mediated mDC and pDC maturation is virus replication independent and, using strand specific PCR, we found no evidence for HCV replication within DCs. Because these effects of HCV on DC subset maturation and function in part recapitulate direct ex vivo analysis of DCs in chronic HCV infection, the mechanisms described here likely account for a portion of the DC subset defects observed in vivo.

show abstract

“…Several studies have reported that mDCs from individuals with chronic HCV infection are defective in inducing the proliferation of allogeneic or antigenspecific T cells (23,25,26,57), while others could not confirm these observations (18,60). Similarly, alpha interferon (IFN-␣) production by pDCs was reported to be impaired in some (23,25,28) but not all (27,29) studies. Such inconsistencies may be due to variable patient demographics or experimental conditions, such as the type of stimuli used to activate DCs (cytokines or TLR agonists), the HCV genotype, the duration of infection, the patient's age and gender, and/or coinfection with other viruses.…”

mentioning

confidence: 99%

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

Pelletier

Bédard

Said

et al. 2013

J Virol

View full text Add to dashboard Cite

Some studies have reported that dendritic cells (DCs) may be dysfunctional in a subset of patients with chronic hepatitis C virus (HCV) infection. However, the function of DCs during acute HCV infection and their role in determining infectious outcome remain elusive. Here, we examined the phenotype and function of myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) during acute HCV infection. Three groups of injection drug users (IDUs) at high risk of HCV infection were studied: an uninfected group, a group with acute HCV infection with spontaneous resolution, and a group with acute infection with chronic evolution. We examined the frequency, maturation status, and cytokine production capacity of DCs in response to the Toll-like receptor 4 (TLR4) and TLR7/8 ligands lipopolysaccharide (LPS) and single-stranded RNA (ssRNA), respectively. Several observations could distinguish HCV-negative IDUs and acute HCV resolvers from patients with acute infection with chronic evolution. First, we observed a decrease in the frequency of mature CD86؉ , programmed death-1 receptor ligand-positive (PDL1 ؉ ), and PDL2 ؉ pDCs. This phenotype was associated with the increased sensitivity of pDCs from resolvers and HCV-negative IDUs versus the group with acute infection with chronic evolution to ssRNA stimulation in vitro. Second, LPS-stimulated mDCs from resolvers and HCV-negative IDUs produced higher levels of cytokines than mDCs from the group with acute infection with chronic evolution. Third, mDCs from all patients with acute HCV infection, irrespective of their outcomes, produced higher levels of cytokines during the early acute phase in response to ssRNA than mDCs from healthy controls. However, this hyperresponsiveness was sustained only in spontaneous resolvers. Altogether, our results suggest that the immature pDC phenotype and sustained pDC and mDC hyperresponsiveness are associated with spontaneous resolution of acute HCV infection.A minor fraction of individuals infected with the hepatitis C virus (HCV) eliminate the virus spontaneously, while the majority develop persistent infection, which may lead to chronic liver diseases (1). Spontaneous resolution of acute HCV infection is associated with the development of a robust and sustained HCV-specific CD4 and CD8 T cell response (2). In contrast, such responses are weak, inefficient, or transient in individuals who develop chronic infection. Several mechanisms underlying this immune failure have been previously described. First, escape mutations in epitopes targeted by virus-specific CD8 ϩ T cells can occur early during acute HCV infection, and this correlates with virus persistence (3-6). Second, failure of HCV-specific CD4 helper T cells to proliferate and produce cytokines was associated with viral recurrence and persistence. This loss of CD4 T cell help may compromise the function of virus-specific CD8 T cells and contribute to the development of suboptimal or exhausted CD8 ϩ T cells (7-13). Dendritic cells (DCs) are the most potent antigen-presenting cells in the body, and ...

show abstract

Comparable functions of plasmacytoid and monocyte-derived dendritic cells in chronic hepatitis C patients and healthy donors

Cited by 98 publications

References 30 publications

Immune responses during acute and chronic infection with hepatitis C virus

Immune responses during acute and chronic infection with hepatitis C virus

Differential Effects of Hepatitis C Virus JFH1 on Human Myeloid and Plasmacytoid Dendritic Cells

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

Contact Info

Product

Resources

About