Differential Expression of Toll-Like Receptors in Dendritic Cells of Patients with Dengue During Early and Late Acute Phases of the Disease

Torres, Silvia; Hernández, Juan Carlos; Giraldo, Diana M.; Arboleda, Margarita; Rojas, Mauricio; Smit, Jolanda M.; Urcuqui-Inchima, Silvio

doi:10.2139/ssrn.2988029

Cited by 11 publications

(14 citation statements)

References 46 publications

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“…These events lead to induction of the anti-viral cytokines IFNs, including IFN-b1, IFN-k1, IFN-k2, and IFN-k3, in human DCs. Interestingly, stimulation with the TLR9 ligand CpG A induces less IFN-a expression in peripheral blood mononuclear cells obtained from DENV-infected patients with severe clinical manifestations compared to those with less severe symptoms [24]. This highlights the crucial role of TLR9 signaling in the pathogenesis of DENV infection.…”

Section: Discussionmentioning

confidence: 92%

Infection with the dengue RNA virus activates TLR9 signaling in human dendritic cells

et al. 2018

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Toll-like receptors (TLRs) are important sensors that recognize pathogen-associated molecular patterns. Generally, TLR9 is known to recognize bacterial or viral DNA but not viral RNA and initiate an immune response. Herein, we demonstrate that infection with dengue virus (DENV), an RNA virus, activates TLR9 in human dendritic cells (DCs). DENV infection induces release of mitochondrial DNA (mtDNA) into the cytosol and activates TLR9 signaling pathways, leading to production of interferons (IFNs). The DENV-induced mtDNA release involves reactive oxygen species generation and inflammasome activation. DENV infection disrupts the association between transcription factor A mitochondria (TFAM) and mtDNA and activates the mitochondrial permeability transition pores. The side-by-side comparison of TLR9 and cyclic GMP-AMP synthase (cGAS) knockdown reveals that both cGAS and TLR9 comparably contribute to DENV-induced immune activation. The significance of TLR9 in DENV-induced immune response is also confirmed in examination with the bone marrow-derived DCs prepared from -knockout mice. Our study unravels a previously unrecognized phenomenon in which infection with an RNA virus, DENV, activates TLR9 signaling by inducing mtDNA release in human DCs.

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Section: Discussionmentioning

confidence: 92%

Infection with the dengue RNA virus activates TLR9 signaling in human dendritic cells

et al. 2018

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“…Igualmente nosotros reportamos en mDC y pDC obtenidas de pacientes con DF, una mayor expresión de TLR3 y TLR9 en fases tempranas de la infección; por el contrario, en pacientes con manifestaciones graves de la enfermedad se evidenció una disminución en la expresión de TLR3 y TLR9 46 .…”

Section: Papel De Las Células Dendríticas Mieloides (Mdc) Y Células Dunclassified

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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“…It was recently reported that DENV NS1 proteins may be recognized by TLR2, TLR4, and TLR6 enhancing the production of proinflammatory cytokines and triggering the endothelial permeability that leads to vascular leakage [ 93 , 94 ]. Interestingly, our group has recently shown a differential expression of TLRs in dendritic cells (DCs) of dengue patients depending on the severity of the disease [ 95 ]. Indeed, there was an increased expression of TLR3 and TLR9 in DCs of patients with DF in contrast to a poor stimulation of both receptors in DCs of patients with DHF.…”

Section: Denv and The Immune Responsementioning

confidence: 99%

Vitamin D-Regulated MicroRNAs: Are They Protective Factors against Dengue Virus Infection?

Arboleda

Urcuqui-Inchima

2016

Advances in Virology

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Over the last few years, an increasing body of evidence has highlighted the critical participation of vitamin D in the regulation of proinflammatory responses and protection against many infectious pathogens, including viruses. The activity of vitamin D is associated with microRNAs, which are fine tuners of immune activation pathways and provide novel mechanisms to avoid the damage that arises from excessive inflammatory responses. Severe symptoms of an ongoing dengue virus infection and disease are strongly related to highly altered production of proinflammatory mediators, suggesting impairment in homeostatic mechanisms that control the host's immune response. Here, we discuss the possible implications of emerging studies anticipating the biological effects of vitamin D and microRNAs during the inflammatory response, and we attempt to extrapolate these findings to dengue virus infection and to their potential use for disease management strategies.

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Differential Expression of Toll-Like Receptors in Dendritic Cells of Patients with Dengue During Early and Late Acute Phases of the Disease

Cited by 11 publications

References 46 publications

Infection with the dengue RNA virus activates TLR9 signaling in human dendritic cells

Infection with the dengue RNA virus activates TLR9 signaling in human dendritic cells

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

Vitamin D-Regulated MicroRNAs: Are They Protective Factors against Dengue Virus Infection?

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