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oai:repository.ucc.edu.co:20.500.12494/496242024-08-20T21:15:54Zcom_20.500.12494_36578com_20.500.12494_36577col_20.500.12494_41230

Arboleda Alzate, J. F. Rodenhuis Zybert, I. A. Hernández López, Juan Carlos Smit, J. M. Urcuqui Inchima, S. 2023-05-24T16:21:34Z 2023-05-24T16:21:34Z 11/10/2017 https://doi.org/10.1371/journal.pntd.0005904 https://www.scopus.com/inward/record.uri?eid=2-s2.0-85032668736&doi=10.1371%2fjournal.pntd.0005904&partnerID=40&md5=fc47c7f8ca16478c0af00e24fff7258b 19352727 https://hdl.handle.net/20.500.12494/49624 Arboleda Alzate J.F.,Rodenhuis-Zybert I.A.,Hernandez Lopez Juan carlos,Smit J.M.,Urcuqui-Inchima S..Human macrophages differentiated in the presence of vitamin D3restrict dengue virus infection and innate responses by downregulating mannose receptor expression.PLOS NEGLECT TROP D. 2017. 11. (10): e0005904 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. 0000-0002-9200-5698 juanc.hernandezl@campusucc.edu.co e0005904 Public Library of Science ADULT ANIMAL ANIMALS ARTICLE BLOOD DONOR BLOOD DONORS CELL DIFFERENTIATION CELL LINE CELL SURFACE RECEPTOR COLECALCIFEROL CULICIDAE CHOLECALCIFEROL DENGUE VIRUS DOWN REGULATION DOWN-REGULATION DRUG EFFECTS ENZYME LINKED IMMUNOSORBENT ASSAY FEMALE FLOW CYTOMETRY GENE EXPRESSION GENE EXPRESSION REGULATION GENETICS HUMAN HUMANS IMMUNE RESPONSE IMMUNITY, INNATE INFLAMMATION INNATE IMMUNITY INTERLEUKIN 10 INTERLEUKIN 1BETA INTERLEUKIN 6 LECTIN LECTINS, C-TYPE MACROPHAGE MACROPHAGES MALE MANNOSE BINDING LECTIN MANNOSE RECEPTOR MANNOSE-BINDING LECTINS METABOLISM MOSQUITO NONHUMAN PHYSIOLOGY REAL TIME POLYMERASE CHAIN REACTION RECEPTORS, CELL S REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION TUMOR NECROSIS FACTOR VIROLOGY VIRUS INFECTION VIRUS PARTICLE VIRUS REPLICATION Human macrophages differentiated in the presence of vitamin D3restrict dengue virus infection and innate responses by downregulating mannose receptor expression Artículo http://purl.org/coar/resource_type/c_6501 http://purl.org/coar/version/c_970fb48d4fbd8a85 info:eu-repo/semantics/article http://purl.org/redcol/resource_type/ART info:eu-repo/semantics/publishedVersion PLOS NEGLECT TROP D info:eu-repo/semantics/openAccess http://purl.org/coar/access_right/c_abf2 Publicationmetadata.only