Please use this identifier to cite or link to this item: http://hdl.handle.net/20.500.12494/41881
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Title: Human macrophages differentiated in the presence of vitamin D3restrict dengue virus infection and innate responses by downregulating mannose receptor expression
Author: Arboleda Alzate J.F.
Rodenhuis-Zybert I.A.
Hernandez Lopez, Juan Carlos
Smit J.M.
Urcuqui-Inchima S.
Email autor: juanc.hernandezl@campusucc.edu.co
Issue Date: 2017
Keywords: colecalciferol
interleukin 10
interleukin 1beta
interleukin 6
mannose receptor
tumor necrosis factor
cell surface receptor
colecalciferol
lectin
mannose binding lectin
mannose receptor
Article
blood donor
Dengue virus
down regulation
enzyme linked immunosorbent assay
flow cytometry
gene expression
immune response
inflammation
innate immunity
nonhuman
real time polymerase chain reaction
reverse transcription polymerase chain reaction
virus infection
virus particle
adult
animal
cell differentiation
cell line
Dengue virus
down regulation
drug effects
female
gene expression regulation
genetics
human
innate immunity
macrophage
male
metabolism
mosquito
physiology
virology
virus replication
Adult
Animals
Blood Donors
Cell Differentiation
Cell Line
Cholecalciferol
Culicidae
Dengue Virus
Down-Regulation
Female
Gene Expression Regulation
Humans
Immunity
Innate
Lectins
C-Type
Macrophages
Male
Mannose-Binding Lectins
Receptors
Cell S
Abstract: Background: Severe dengue disease is associated with high viral loads and overproduction of pro-inflammatory cytokines, suggesting impairment in the control of dengue virus (DENV) and the mechanisms that regulate cytokine production. Vitamin D3has been described as an important modulator of immune responses to several pathogens. Interestingly, increasing evidence has associated vitamin D with decreased DENV infection and early disease recovery, yet the molecular mechanisms whereby vitamin D reduces DENV infection are not well understood. Methods and principal findings: Macrophages represent important cell targets for DENV replication and consequently, they are key drivers of dengue disease. In this study we evaluated the effect of vitamin D3on the differentiation of monocyte-derived macrophages (MDM) and their susceptibility and cytokine response to DENV. Our data demonstrate that MDM differentiated in the presence of vitamin D3(D3-MDM) restrict DENV infection and moderate the classical inflammatory cytokine response. Mechanistically, vitamin D3-driven differentiation led to reduced surface expression of C-type lectins including the mannose receptor (MR, CD206) that is known to act as primary receptor for DENV attachment on macrophages and to trigger of immune signaling. Consequently, DENV bound less efficiently to vitamin D3-differentiated macrophages, leading to lower infection. Interestingly, IL-4 enhanced infection was reduced in D3-MDM by restriction of MR expression. Moreover, we detected moderate secretion of TNF-a, IL-1ß, and IL-10 in D3-MDM, likely due to less MR engagement during DENV infection. Conclusions/Significance: Our findings reveal a molecular mechanism by which vitamin D counteracts DENV infection and progression of severe disease, and indicates its potential relevance as a preventive or therapeutic candidate. © 2017 Arboleda Alzate et al.
Type: Artículo
Citation: Arboleda JF,Rodenhuis IA,Hernández JC,Smit JM,Urcuqui S. Human macrophages differentiated in the presence of vitamin D3restrict dengue virus infection and innate responses by downregulating mannose receptor expression. PLoS Negl Trop Dis. 2017. 11. (10):e0005904. .
Other Identifiers: https://doi.org/10.17533/udea.boan.v32n53a09
Appears in Collections:Artículos Científicos

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