Characterisation of dendritic cell frequency and phenotype in bovine afferent lymph reveals kinetic changes in costimulatory molecule expression

ABSTRACT The paramyxovirus simian virus 5 (SV5) is a poor activator of human dendritic cell (DC) maturation pathways in vitro, and infected DC do not upregulate cell surface costimulatory proteins or secretion of immunomodulatory cytokines. We evaluated the hypothesis that activation of SV5-infected DC would be enhanced by engineering SV5 to express a Toll-like-receptor (TLR) ligand. To test this hypothesis, a novel virus was engineered such that the gene encoding an intracellular form of the TLR5 ligand flagellin was expressed from the genome of wild-type (WT) SV5 (SV5-flagellin). Cells infected in vitro with the flagellin-expressing virus released low levels of biologically active flagellin, which was capable of stimulating TLR5 signaling. Infection of human peripheral blood mononuclear cell-derived immature DC with SV5-flagellin resulted in enhanced levels of interleukin-6 (IL-6) and IL-12 compared to infection with DC with the parental virus, WT SV5. In contrast to cytokine induction, the flagellin-expressing virus did not appreciably increase DC surface expression of the costimulatory molecule CD80 or CD86 above the level seen with WT SV5 alone. In mixed-culture assays, DC infected with the flagellin-expressing virus were more effective at activating gamma interferon secretion from both CD8+ and CD4+ allogeneic T cells than DC infected with WT SV5. Our results with SV5-directed intracellular expression of flagellin may be applicable to other vectors or pathogenic viruses where overcoming impairment of DC activation could contribute to the development of safer and more effective vaccines.

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Costimulatory molecule-deficient dendritic cell progenitors induce T cell hyporesponsiveness in vitro prolong the survival of vascularized cardiac allografts

Transplantation Proceedings ◽

10.1016/s0041-1345(96)00532-5 ◽

1997 ◽

Vol 29 (1-2) ◽

pp. 1310 ◽

Cited By ~ 14

Author(s):

F. Fu ◽

Y. Li ◽

S. Qian ◽

L. Lu ◽

F.D. Chambers ◽

...

Keyword(s):

T Cell ◽

Dendritic Cell ◽

Costimulatory Molecule ◽

Cardiac Allografts

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Echinococcus granulosus Antigen B Impairs Human Dendritic Cell Differentiation and Polarizes Immature Dendritic Cell Maturation towards a Th2 Cell Response

Infection and Immunity ◽

10.1128/iai.01156-06 ◽

2007 ◽

Vol 75 (4) ◽

pp. 1667-1678 ◽

Cited By ~ 90

Author(s):

Rachele Riganò ◽

Brigitta Buttari ◽

Elisabetta Profumo ◽

Elena Ortona ◽

Federica Delunardo ◽

...

Keyword(s):

Dendritic Cell ◽

Echinococcus Granulosus ◽

Therapeutic Option ◽

Costimulatory Molecule ◽

Lower Percentage ◽

Th2 Response ◽

Monocyte Differentiation ◽

Dendritic Cell Differentiation ◽

Antigen B ◽

Dc Maturation

ABSTRACT Despite inducing a strong host cellular and humoral immune response, the helminth Echinococcus granulosus is a highly successful parasite that develops, progresses, and ultimately causes chronic disease. Although surgery remains the preferred therapeutic option, pharmacological research now envisages antihelminthic strategies. To understand the mechanisms that E. granulosus uses to escape host immunosurveillance and promote chronic infection, we investigated how two hydatid cyst components, purified antigen B (AgB) and sheep hydatid fluid (SHF), act on host dendritic cell (DC) differentiation from monocyte precursors and how they influence maturation of DC that have already differentiated. We evaluated the immunomodulatory potential of these antigens by performing immunochemical and cytofluorimetric analyses of monocyte-derived DCs from healthy human donors. During monocyte differentiation, AgB and SHF downmodulated CD1a expression and upregulated CD86 expression. Compared with immature DCs differentiated in medium alone (iDCs), AgB- and SHF-differentiated cells stimulated with lipopolysaccharide included a significantly lower percentage of CD83+ cells (P < 10−4) and had weaker costimulatory molecule expression. When stimulated with AgB and SHF, iDCs matured and primed lymphocytes towards the Th2 response typical of E. granulosus infection. SHF and particularly AgB reduced the production of interleukin-12p70 (IL-12p70) and tumor necrosis factor alpha in lipopolysaccharide-stimulated iDCs. Anti-IL-10 antibodies increased the levels of IL-12p70 secretion in AgB- and SHF-matured DCs. AgB and SHF induced interleukin-1 receptor-associated kinase phosphorylation and activated nuclear factor-κB, suggesting that Toll-like receptors could participate in E. granulosus-stimulated DC maturation. These results suggest that E. granulosus escapes host immunosurveillance in two ways: by interfering with monocyte differentiation and by modulating DC maturation.

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Pneumocystis Cell Wall β-Glucans Induce Dendritic Cell Costimulatory Molecule Expression and Inflammatory Activation through a Fas-Fas Ligand Mechanism

The Journal of Immunology ◽

10.4049/jimmunol.177.1.459 ◽

2006 ◽

Vol 177 (1) ◽

pp. 459-467 ◽

Cited By ~ 45

Author(s):

Eva M. Carmona ◽

Robert Vassallo ◽

Zvezdana Vuk-Pavlovic ◽

Joseph E. Standing ◽

Theodore J. Kottom ◽

...

Keyword(s):

Cell Wall ◽

Dendritic Cell ◽

Fas Ligand ◽

Costimulatory Molecule ◽

Inflammatory Activation

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Blood Dendritic Cell Frequency Declines in Idiopathic Parkinson’s Disease and Is Associated with Motor Symptom Severity

PLoS ONE ◽

10.1371/journal.pone.0065352 ◽

2013 ◽

Vol 8 (6) ◽

pp. e65352 ◽

Cited By ~ 13

Author(s):

Antonio Ciaramella ◽

Francesca Salani ◽

Federica Bizzoni ◽

Francesco E. Pontieri ◽

Alessandro Stefani ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Dendritic Cell ◽

Symptom Severity ◽

Motor Symptom ◽

Idiopathic Parkinson’S Disease ◽

Cell Frequency ◽

Idiopathic Parkinson's Disease ◽

Blood Dendritic Cell

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TACI-BLyS signaling via B-cell–dendritic cell cooperation is required for naive CD8+ T-cell priming in vivo

Blood ◽

10.1182/blood-2004-12-4708 ◽

2006 ◽

Vol 107 (2) ◽

pp. 594-601 ◽

Cited By ~ 31

Author(s):

Yaiza Diaz-de-Durana ◽

George T. Mantchev ◽

Richard J. Bram ◽

Alessandra Franco

Keyword(s):

B Cells ◽

Dendritic Cell ◽

B Cell ◽

B Lymphocyte ◽

Costimulatory Molecule ◽

Early Signal ◽

Maturation In Vitro ◽

Deficient Mice

AbstractWe demonstrated that B-cell–dendritic cell (DC) interactions via transmembrane activator and calcium modulator and cyclophilin ligand (CAML) interactor (TACI) and B-lymphocyte stimulator (BLyS) provide an early signal critical to generate adequate numbers of mature antigen presenting cells (APCs) to prime naive CD8+ T cells (CTLs) in vivo. Evidence that B cells are required for efficient CTL generation in mice and that reconstitution with wild-type but not TACI-knockout B cells restored normal CTL responses support our conclusion. Moreover, low doses of a TACI fusion protein (TACI-Fc) that express the extracellular domain of TACI (amino acid [aa] 1-126) restored CTL priming in B-cell–deficient mice in vivo and induced DC maturation in vitro. In fact, following interactions with B cells, splenic DCs rapidly express the CD86 costimulatory molecule, to an extent comparable to the exposure to antigenic stimuli. BLyShigh peptide-pulsed bone marrow–derived DCs, used as vaccines in vivo, cannot generate CTLs in B-cell–deficient and TACI-deficient mice, strongly supporting a need for B-cell–DC cooperation through TACI-BLyS during CTL first encounter with antigens in vivo.

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The Effect of Chronic Hepatitis B Virus Infection on BDCA3+ Dendritic Cell Frequency and Function

PLoS ONE ◽

10.1371/journal.pone.0161235 ◽

2016 ◽

Vol 11 (8) ◽

pp. e0161235 ◽

Cited By ~ 9

Author(s):

Evelyn van der Aa ◽

Sonja I. Buschow ◽

Paula J. Biesta ◽

Harry L. A. Janssen ◽

Andrea M. Woltman

Keyword(s):

Chronic Hepatitis ◽

Hepatitis B Virus ◽

Dendritic Cell ◽

Virus Infection ◽

Hepatitis B ◽

Hepatitis B Virus Infection ◽

Cell Frequency ◽

Chronic Hepatitis B Virus ◽

B Virus ◽

And Function

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Rapamycin inhibits IL-4—induced dendritic cell maturation in vitro and dendritic cell mobilization and function in vivo

Blood ◽

10.1182/blood-2002-11-3370 ◽

2003 ◽

Vol 101 (11) ◽

pp. 4457-4463 ◽

Cited By ~ 270

Author(s):

Holger Hackstein ◽

Timucin Taner ◽

Alan F. Zahorchak ◽

Adrian E. Morelli ◽

Alison J. Logar ◽

...

Keyword(s):

T Cell ◽

Dendritic Cell ◽

Transplant Rejection ◽

Costimulatory Molecule ◽

Interleukin 2 ◽

Hematologic Malignancies ◽

Dendritic Cell Maturation ◽

Murine Bone Marrow

Abstract Rapamycin (RAPA) is a potent immunosuppressive macrolide hitherto believed to mediate its action primarily via suppression of lymphocyte responses to interleukin 2 (IL-2) and other growth factors. We show here that this view is incomplete and provide evidence that RAPA suppresses the functional activation of dendritic cells (DCs) both in vitro and in vivo. In vitro, RAPA inhibits IL-4—dependent maturation and T-cell stimulatory activity of murine bone marrow—derived DCs. These effects are associated with posttranscriptional down-regulation of both subunits of the IL-4 receptor complex (CD124, CD132) and are mediated via binding of RAPA to its intracellular receptor FK506-binding protein 12 (FKBP12). In vivo, RAPA impairs steady-state DC generation and fms-like tyrosine 3 kinase ligand (Flt3L)—induced DC mobilization. In addition, in vivo administration of RAPA impairs DC costimulatory molecule up-regulation, production of proinflammatory cytokines, and T-cell allostimulatory capacity. These novel findings have implications for RAPA-based therapy of chronic DC-triggered autoimmune diseases, transplant rejection, and hematologic malignancies with activating Flt3 mutations.

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