Dengue Virus Activates Membrane TRAIL Relocalization and IFN-α Production by Human Plasmacytoid Dendritic Cells In Vitro and In Vivo

Gandini, Mariana; Gras, Christophe; Azeredo, Elzinandes Leal de; Pinto, Luciana Wernersbach; Smith, Nikaïa; Desprès, Philippe; Cunha, Rivaldo Venâncio da; Souza, Luíz José de; Kubelka, Claire Fernandes; Herbeuval, Jean-Philippe

doi:10.1371/journal.pntd.0002257

Cited by 53 publications

(62 citation statements)

References 79 publications

(103 reference statements)

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“…6A). Previously, sTRAIL has been attributed to an antiviral mechanism in dengue, given by the induction of apoptosis or the production of type I IFN (47), reducing the cellular viral burden (35) and thus explaining the higher levels of sTRAIL found in children who did not develop severe forms of the infection (Fig. 6A) (36,48).…”

Section: Discussionmentioning

confidence: 96%

Viability and Functionality of Cryopreserved Peripheral Blood Mononuclear Cells in Pediatric Dengue

Perdomo‐Celis

Salgado

Castañeda

et al. 2016

Clin Vaccine Immunol

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bCryopreserved peripheral blood mononuclear cells (PBMCs) are widely used in studies of dengue. In this disease, elevated frequency of apoptotic PBMCs has been described, and molecules such as soluble tumor necrosis factor (TNF)-related apoptosisinducing ligands (sTRAIL) are involved. This effect of dengue may affect the efficiency of PBMC cryopreservation. Here, we evaluate the viability (trypan blue dye exclusion and amine-reactive dye staining) and functionality (frequency of gamma interferon [IFN-␥]-producing T cells after polyclonal stimulation) of fresh and cryopreserved PBMCs from children with dengue (in acute and convalescence phases), children with other febrile illnesses, and healthy children as controls. Plasma sTRAIL levels were also evaluated. The frequencies of nonviable PBMCs detected by the two viability assays were positively correlated (r ‫؍‬ 0.74; P < 0.0001). Cryopreservation particularly affected the PBMCs of children with dengue, who had a higher frequency of nonviable cells than healthy children and children with other febrile illnesses (P < 0.02), and PBMC viability levels were restored in the convalescent phase. In the acute phase, an increased frequency of CD3 ؉ CD8 ؉ amine-positive cells was found before cryopreservation (P ‫؍‬ 0.01). Except for B cells in the acute phase, cryopreservation usually did not affect the relative frequencies of viable PBMC subpopulations. Dengue infection reduced the frequency of IFN-␥-producing CD3؉ cells after stimulation compared with healthy controls and convalescent-phase patients (P < 0.003), and plasma sTRAIL correlated with this decreased frequency in dengue (rho ‫؍‬ ؊0.56; P ‫؍‬ 0.01). Natural dengue infection in children can affect the viability and functionality of cryopreserved PBMCs. Cryopreservation is the maintenance of cells and biological tissues at low temperatures and is based on the use of various media or solutions that form hydrogen bonds with water molecules, preventing cellular damage. The low temperatures allow the cells to enter a quiescent state in which cellular functions are suspended without affecting their intrinsic characteristics (1). Peripheral blood mononuclear cells (PBMCs) are frequently cryopreserved for use in transplants or immunological studies (2, 3). However, the cryopreservation process may affect viability, phenotype, and cellular functionality due to factors such as inadequate temperatures, the freezing protocol used, the expertise of the personnel, and freezing time (4, 5). The disease of the individual from whom the PBMCs come also affects cryopreservation. For example, PBMCs from subjects infected with human immunodeficiency virus (HIV) presented reduced viability after cryopreservation, possibly due to the increased numbers of apoptotic cells circulating during the course of the disease (6). Similar findings have been found in the acute phases of diseases, such as visceral leishmaniasis (7). Particularly for HIV, great efforts have been undertaken to optimize the evaluation and comparability of immune tests...

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Section: Discussionmentioning

confidence: 96%

Viability and Functionality of Cryopreserved Peripheral Blood Mononuclear Cells in Pediatric Dengue

Perdomo‐Celis

Salgado

Castañeda

et al. 2016

Clin Vaccine Immunol

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“…Interestingly, Trail − / − mice are unable to clear an IAV infection as well as wild-type mice, and Trail − / − mice are more susceptible to death from immunopathology after IAV infection (Brincks et al, 2008; Brincks et al, 2011). Additional data report increased TRAIL expression after infection with Dengue virus, hepatitis virus, human immunodeficiency virus, measles virus, respiratory syncytial virus, and West Nile virus contributes to both viral clearance and immunopathology (Bem et al, 2010; Stegmann et al, 2010; van Grevenynghe et al, 2011; Barblu et al, 2012; Shrestha et al, 2012; Abdullah et al, 2013; Gandini et al, 2013; Gras et al, 2013; Werner et al, 2013; Brost et al, 2014; Limonta et al, 2014). …”

Section: Immunotherapy Involving Trail Receptor Agonists In Non-camentioning

confidence: 98%

Therapeutic applications of TRAIL receptor agonists in cancer and beyond

Amarante-Mendes

Griffith

2015

Pharmacology & Therapeutics

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TRAIL/Apo-2L is a member of the TNF superfamily first described as an apoptosis-inducing cytokine in 1995. Similar to TNF and Fas ligand, TRAIL induces apoptosis in caspase-dependent manner following TRAIL death receptor trimerization. Because tumor cells were shown to be particularly sensitive to this cytokine while normal cells/tissues proved to be resistant along with being able to synthesize and release TRAIL, it was rapidly appreciated that TRAIL likely served as one of our major physiologic weapons against cancer. In line with this, a number of research laboratories and pharmaceutical companies have attempted to exploit the ability of TRAIL to kill cancer cells by developing recombinant forms of TRAIL or TRAIL receptor agonists (e.g., receptor-specific mAb) for therapeutic purposes. In this review article we will describe the biochemical pathways used by TRAIL to induce different cell death programs. We will also summarize the clinical trials related to this pathway and discuss possible novel uses of TRAIL-related therapies. In recent years, the physiological importance of TRAIL has expanded beyond being a tumoricidal molecule to one critical for a number of clinical settings — ranging from infectious disease and autoimmunity to cardiovascular anomalies. We will also highlight some of these conditions where modulation of the TRAIL/TRAIL receptor system may be targeted in the future.

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“…Rather than autoantibody-induced cell death, several studies have focused on the apoptosis that is directly induced by DENV infections (52)(53)(54). Studies have demonstrated that DENV infections elicit proapoptotic responses involving the suppression of Bcl-2 and Bcl-x L as well as the induction of Bax (40)(41)(42).…”

Section: Discussionmentioning

confidence: 99%

Endothelial Cell Sensitization by Death Receptor Fractions of an Anti–Dengue Nonstructural Protein 1 Antibody Induced Plasma Leakage, Coagulopathy, and Mortality in Mice

Sun

Chang

Lien

et al. 2015

The Journal of Immunology

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The mechanisms leading to the life-threatening dengue hemorrhagic fever (DHF) remain elusive. DHF preferentially occurs during secondary dengue infections, suggesting that aberrant immune responses are involved in its development. We previously demonstrated that the autoantibodies elicited by dengue virus (DENV) nonstructural protein 1 (NS1; anti–NS1 Igs) induce plasma leakage and mortality in mice with warfarinized anticoagulant suppression. However, the involved pathogenic Ig fractions of anti–NS1 Igs remain unclear. In this study, the autoreactive Igs in patients with DHF and in NS1-immunized rabbits crossreacted with TNF-related apoptosis-inducing ligand receptor 1 (death receptor [DR]4). Challenges with the DENV in a subcytotoxic dose sensitized endothelial cells to apoptosis. Treatments with the autoantibodies induced proapoptotic activities and suppressed the surface expression of endothelial anticoagulant thrombomodulin. Combined treatments comprising the DENV and DR4 affinity-purified fractions of anti–NS1 IgGs (anti–NS1-DR4 Ig), but not preimmune control IgGs, in subcytotoxic doses led to apoptosis in endothelial cells. Treatments with the anti–NS1-DR4 Ig led to plasma leakage, coagulopathy, and morality in mice with warfarinized anticoagulant suppression. These results suggest that DR4-induced endothelial cell sensitization through NS1-elicited autoantibodies exacerbates anticoagulant suppression, vascular injury, and plasma leakage. Detecting and blocking anti–DR Igs in patients may be novel strategies for managing severe DENV infection.

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Dengue Virus Activates Membrane TRAIL Relocalization and IFN-α Production by Human Plasmacytoid Dendritic Cells In Vitro and In Vivo

Cited by 53 publications

References 79 publications

Viability and Functionality of Cryopreserved Peripheral Blood Mononuclear Cells in Pediatric Dengue

Viability and Functionality of Cryopreserved Peripheral Blood Mononuclear Cells in Pediatric Dengue

Therapeutic applications of TRAIL receptor agonists in cancer and beyond

Endothelial Cell Sensitization by Death Receptor Fractions of an Anti–Dengue Nonstructural Protein 1 Antibody Induced Plasma Leakage, Coagulopathy, and Mortality in Mice

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