CD40 Ligand Enhances Dengue Viral Infection of Dendritic Cells: A Possible Mechanism for T Cell-Mediated Immunopathology

Sun, Peifang; Celluzzi, Christina M.; Marovich, Mary; Subramanian, Hemavathy; Eller, Michael A.; Widjaja, Susana; Palmer, Dupeh R.; Porter, Kevin R.; Sun, Wellington; Burgess, Timothy

doi:10.4049/jimmunol.177.9.6497

Cited by 32 publications

(29 citation statements)

References 57 publications

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“…For (C), the staining isotype control is depicted in Fig. 4D infected DC by providing an early source of IFN-g (19), or CD40-CD40L signals during NK-DC interactions (53). NK cells might also enhance the release of DenV Ag by cytolysis of DenV-infected DC, and so promote subsequent DC-mediated Ag cross-presentation.…”

Section: Discussionmentioning

confidence: 99%

The Combination of Type I IFN, TNF-α, and Cell Surface Receptor Engagement with Dendritic Cells Enables NK Cells To Overcome Immune Evasion by Dengue Virus

Lim

Yawata

Selva

et al. 2014

The Journal of Immunology

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Clinical studies have suggested the importance of the NK cell response against dengue virus (DenV), an arboviral infection that afflicts >50 million individuals each year. However, a comprehensive understanding of the NK cell response against dengue-infected cells is lacking. To characterize cell-contact mechanisms and soluble factors that contribute to the antidengue response, primary human NK cells were cocultured with autologous DenV-infected monocyte-derived dendritic cells (DC). NK cells responded by cytokine production and the lysis of target cells. Notably, in the absence of significant monokine production by DenV-infected DC, it was the combination of type I IFNs and TNF-α produced by DenV-infected DC that was important for stimulating the IFN-γ and cytotoxic responses of NK cells. Cell-bound factors enhanced NK cell IFN-γ production. In particular, reduced HLA class I expression was observed on DenV-infected DC, and IFN-γ production was enhanced in licensed/educated NK cell subsets. NK–DC cell contact was also identified as a requirement for a cytotoxic response, and there was evidence for both perforin/granzyme as well as Fas/Fas ligand–dependent pathways of killing by NK cells. In summary, our results have uncovered a previously unappreciated role for the combined effect of type I IFNs, TNF-α, and cell surface receptor–ligand interactions in triggering the antidengue response of primary human NK cells.

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Section: Discussionmentioning

confidence: 99%

The Combination of Type I IFN, TNF-α, and Cell Surface Receptor Engagement with Dendritic Cells Enables NK Cells To Overcome Immune Evasion by Dengue Virus

Lim

Yawata

Selva

et al. 2014

The Journal of Immunology

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“…Following the bite of an infected Aedes mosquito, the initial local viral replication is believed to take place in the skin DCs, including myeloid DCs and Langerhans cells (31,53,59). Dengue-infected DCs play a key role in the immunopathogenesis of DHF/DSS, as, along with macrophages, they release proinflammatory cytokines and soluble factors that mediate plasma leakage, thrombocytopenia, and hypovolemic shock associated with severe dengue infection (14,15,29,38).…”

mentioning

confidence: 99%

Targeted Delivery of Small Interfering RNA to Human Dendritic Cells To Suppress Dengue Virus Infection and Associated Proinflammatory Cytokine Production

Subramanya

Kim

Abraham

et al. 2010

J Virol

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Dengue is a common arthropod-borne flaviviral infection in the tropics, for which there is no vaccine or specific antiviral drug. The infection is often associated with serious complications such as dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS), in which both viral and host factors have been implicated. RNA interference (RNAi) is a potent antiviral strategy and a potential therapeutic option for dengue if a feasible strategy can be developed for delivery of small interfering RNA (siRNA) to dendritic cells (DCs) and macrophages, the major in vivo targets of the virus and also the source of proinflammatory cytokines. Here we show that a dendritic cell-targeting 12-mer peptide ( Dengue is a mosquito-borne flavivirus infection that has emerged as a serious public health problem worldwide. Four serotypes of dengue virus (DEN-1 to DEN-4) are capable of causing human disease varying in severity from acute selflimiting febrile illness to life-threatening dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). The plasma leakage, hemorrhagic manifestations, and shock that characterize DHF/DSS are considered to have an immunological basis, as they are more common during secondary infection with a heterologous dengue virus strain (15,28,33). However, severe clinical manifestations can also occur during primary dengue infection, pointing to a contributory role of viral virulence factors. The WHO estimates that more than 20,000 people worldwide, mainly children, die each year from serious complications of dengue. No specific antiviral therapies are currently available for treating the infection, and efforts to develop a safe prophylactic vaccine have been hindered by the complex role of the immune system in disease pathogenesis (39,52,57). Thus, novel treatment strategies that block viral replication and/or to attenuate the exaggerated cytokine response associated with DHF/DSS complications are urgently needed.Potent and specific gene silencing mediated by RNA interference (RNAi) has generated a great deal of interest in development of RNAi as a therapeutic strategy against viral infections (50,54). Many studies have demonstrated the effectiveness of the RNAi approach to suppress flavivirus infection, including dengue virus replication in experimental cell lines (3,23,26,42,60). In addition, the versatility of RNAi could also be exploited to block important host mediators that contribute to dengue pathogenesis. However, the existence of * Corresponding author. Present address:

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“…El TNF-α e IFN-α pueden generar la maduración de DC adyacentes, pero a la vez altas concentraciones de IL-10 puede desencadenar un fenotipo regulador de DC, disminuyendo la activación de la respuesta inmune, lo cual ha sido relacionado con la gravedad de la infección por DENV 55 . Por otra parte, los linfocitos T cumplen su función co-estimuladora de DC a través de CD40L, IL-6, IFN-ɣ y TNF-α 59 . Esto es muy interesante porque recientemente se describió que las DC obtenidas de pacientes infectados con DENV producen gran cantidad de quimoquinas inducibles por IFN-ɣ (CXCL9, CXCL10 y CXCL11), lo que influye directamente en la permeabilidad endotelial y, por ende, muy posiblemente en la patogénesis del DENV 60 .…”

Section: Consecuencias De La Infección De DC Por Denvunclassified

Papel de las células dendríticas en la infección por el virus dengue: blancos de replicación y respuesta inmune

Martínez

Hernández

Urcuqui-Inchima

2017

Rev. chil. infectol.

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CD40 Ligand Enhances Dengue Viral Infection of Dendritic Cells: A Possible Mechanism for T Cell-Mediated Immunopathology

Cited by 32 publications

References 57 publications

The Combination of Type I IFN, TNF-α, and Cell Surface Receptor Engagement with Dendritic Cells Enables NK Cells To Overcome Immune Evasion by Dengue Virus

The Combination of Type I IFN, TNF-α, and Cell Surface Receptor Engagement with Dendritic Cells Enables NK Cells To Overcome Immune Evasion by Dengue Virus

Targeted Delivery of Small Interfering RNA to Human Dendritic Cells To Suppress Dengue Virus Infection and Associated Proinflammatory Cytokine Production

Papel de las células dendríticas en la infección por el virus dengue: blancos de replicación y respuesta inmune

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