Quantitative and functional defects of dendritic cells in classic Kaposi's sarcoma

Bella, Silvia Della; Nicola, Stefania; Brambilla, Lucia; Riva, Antonio; Ferrucci, Silvia; Presicce, Pietro; Boneschi, Vinicio; Berti, Emilio; Villa, Maria Luisa

doi:10.1016/j.clim.2006.01.011

Cited by 56 publications

(28 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…DC function is notably altered in KS, PEL, and MCD cases as previously described in this review, and the impact of direct HHV-8 infection of DC (Chan et al, 2001; Della Bella et al, 2006; Cirone et al, 2008) correlates with a dampening of DC functionality. A recent report suggests that one manner by which HHV-8 alters DC function is by blocking autophagy, a type of non-apoptotic programmed cell death, through STAT3 activation and the production of IL-6, IL-10, and IL-23 in MDDC in vitro (Santarelli et al, 2014).…”

Section: Effect Of Hhv-8 Infection On DCsupporting

confidence: 64%

“…DC quantity and functional quality are lowered or skewed in classic KS patients. These patients present with a lower frequency of MDDC and pDC, as well as an up-regulation of the endocytic receptor CD91 and decrease in expression of the T cell maturation factor IL-12 compared to HHV-8 positive individuals without KS (Della Bella et al, 2006). The likelihood of KS development and time to progression after HHV-8 seroconversion varies based on history of previous infections, HIV-1 co-infection, and behavioral characteristics (Armenian et al, 1993).…”

Section: In Hhv-8-associated Diseasementioning

confidence: 99%

See 1 more Smart Citation

Dendritic cells: key players in human herpesvirus 8 infection and pathogenesis

et al. 2014

View full text Add to dashboard Cite

Human herpesvirus 8 (HHV-8; Kaposi's sarcoma-associated herpesvirus) is an oncogenic gammaherpesvirus that primarily infects cells of the immune and vascular systems. HHV-8 interacts with and targets professional antigen presenting cells and influences their function. Infection alters the maturation, antigen presentation, and immune activation capabilities of certain dendritic cells (DC) despite non-robust lytic replication in these cells. DC sustains a low level of antiviral functionality during HHV-8 infection in vitro. This may explain the ability of healthy individuals to effectively control this virus without disease. Following an immune compromising event, such as organ transplantation or human immunodeficiency virus type 1 infection, a reduced cellular antiviral response against HHV-8 compounded with skewed DC cytokine production and antigen presentation likely contributes to the development of HHV-8 associated diseases, i.e., Kaposi's sarcoma and certain B cell lymphomas. In this review we focus on the role of DC in the establishment of HHV-8 primary and latent infection, the functional state of DC during HHV-8 infection, and the current understanding of the factors influencing virus-DC interactions in the context of HHV-8-associated disease.

show abstract

Section: Effect Of Hhv-8 Infection On DCsupporting

confidence: 64%

Section: In Hhv-8-associated Diseasementioning

confidence: 99%

Dendritic cells: key players in human herpesvirus 8 infection and pathogenesis

et al. 2014

View full text Add to dashboard Cite

show abstract

“…It has proven anti-apoptotic effects on B cells [38], [39] and it is expressed by a multitude of cell types upon HHV-8 infection [40], [41]. We ourselves previously demonstrated that dendritic cells from cKS patients produce higher amounts of IL-6 than controls [42]. The lack of increased human-IL-6 levels in our patients and the lack of correlation between circulating IL-6 and B cell changes cannot rule out either the involvement of v-IL-6 or a local effect exerted by IL-6 within lymphoid tissues, namely the spleen.…”

Section: Discussionmentioning

confidence: 98%

Human Herpesvirus-8 Infection Leads to Expansion of the Preimmune/Natural Effector B Cell Compartment

et al. 2010

Self Cite

View full text Add to dashboard Cite

BackgroundHuman herpesvirus-8 (HHV-8) is the etiological agent of Kaposi's sarcoma (KS) and of some lymphoproliferative disorders of B cells. Most malignancies develop after long-lasting viral dormancy, and a preventing role for both humoral and cellular immune control is suggested by the high frequency of these pathologies in immunosuppressed patients. B cells, macrophages and dendritic cells of peripheral lymphoid organs and blood represent the major reservoir of HHV-8. Due to the dual role of B cells in HHV-8 infection, both as virus reservoir and as agents of humoral immune control, we analyzed the subset distribution and the functional state of peripheral blood B cells in HHV-8-infected individuals with and without cKS.Methodology/Principal FindingsCirculating B cells and their subsets were analyzed by 6-color flow cytometry in the following groups: 1- patients HHV-8 positive with classic KS (cKS) (n = 47); 2- subjects HHV-8 positive and cKS negative (HSP) (n = 10); 3- healthy controls, HHV-8 negative and cKS negative (HC) (n = 43). The number of B cells belonging to the preimmune/natural effector compartment, including transitional, pre-naïve, naïve and MZ-like subsets, was significantly higher among HHV-8 positive subjects, with or without cKS, while was comparable to healthy controls in the antigen-experienced T-cell dependent compartment. The increased number of preimmune/natural effector B cells was associated with increased resistance to spontaneous apoptosis, while it did not correlate with HHV-8 viral load.Conclusions/SignificanceOur results indicate that long-lasting HHV-8 infection promotes an imbalance in peripheral B cell subsets, perturbing the equilibrium between earlier and later steps of maturation and activation processes. This observation may broaden our understanding of the complex interplay between viral and immune factors leading HHV-8-infected individuals to develop HHV-8-associated malignancies.

show abstract

“…81,82 STAT3 activation by KSHV could occur also in vivo and be responsible for the functional impairment of DCs observed in patients with Kaposi sarcoma. 83,84 Several KSHV proteins may inhibit autophagy at different steps in different cell types. 18 A key role in such inhibition has been clearly demonstrated for v-BCL2, 31,32 v-CFLAR/ FLIP 28,29 and K7.…”

Section: 53mentioning

confidence: 99%

KSHV reduces autophagy in THP-1 cells and in differentiating monocytes by decreasing CAST/calpastatin and ATG5 expression

et al. 2016

View full text Add to dashboard Cite

We have previously shown that Kaposi sarcoma-associated herpesvirus (KSHV) impairs monocyte differentiation into dendritic cells (DCs). Macroautophagy/autophagy has been reported to be essential in such a differentiating process. Here we extended these studies and found that the impairment of DC formation by KSHV occurs through autophagy inhibition. KSHV indeed reduces CAST (calpastatin) and consequently decreases ATG5 expression in both THP-1 monocytoid cells and primary monocytes. We unveiled a new mechanism put in place by KSHV to escape from immune control. The discovery of viral immune suppressive strategies that contribute to the onset and progression of viral-associated malignancies is of fundamental importance for finding new therapeutic approaches against them.

show abstract

Quantitative and functional defects of dendritic cells in classic Kaposi's sarcoma

Cited by 56 publications

References 36 publications

Dendritic cells: key players in human herpesvirus 8 infection and pathogenesis

Dendritic cells: key players in human herpesvirus 8 infection and pathogenesis

Human Herpesvirus-8 Infection Leads to Expansion of the Preimmune/Natural Effector B Cell Compartment

KSHV reduces autophagy in THP-1 cells and in differentiating monocytes by decreasing CAST/calpastatin and ATG5 expression

Contact Info

Product

Resources

About