Innate immune response during DENV-2 infection of monocytes/macrophages

dc.contributorUrcuqui-Inchima, Silvio
dc.contributorSmit, Jolanda
dc.contributorRodenhuis-Zybert, Izabela
dc.creatorCastillo Ramírez, Jorge Andrés
dc.date2022-05-31T18:23:27Z
dc.date2022-05-31T18:23:27Z
dc.date2022
dc.date.accessioned2023-08-28T20:16:43Z
dc.date.available2023-08-28T20:16:43Z
dc.identifierhttp://hdl.handle.net/10495/28814
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8476609
dc.descriptionABSTRACT: The pathogenesis of DENV infection is characterized by a dysregulated inflammatory response and a transient increase in endothelial permeability. Monocytes and macrophages play an essential role during innate immune response against DENV infection, as they are innate sentinels and contribute to viral clearance. Nevertheless, they also contribute to systemic inflammation by producing high levels of soluble factors. This thesis aimed to dissect the role of some innate immune sensors in DENV sensing and induction of inflammatory response of monocytes/macrophages and how this response can be modulated by immunomodulators such as VitD3 and LL-37. By sorting monocyte subsets from PBMCs, we found that TLR2 mediated DENV-2 replication and inflammatory response in classical monocytes, while DENV-2 infection and immune response in non-classical monocytes was mediated by other receptors. Also, TLR2-mediated inflammatory response mediated endothelial dysfunction, underlying the role of classical monocyte in DENV pathogenesis. Vitamin D (VitD3) is known to regulate inflammation and increase antimicrobial peptides expression. Therefore, we evaluated the regulation of innate immune response by VitD3 in monocyte-derived macrophages (MDMs). Differentiation of MDMs in the presence of VitD3 down-regulated the expression of IL-6, TNF-α, RIG-I, TLR3, TLR7, TLR9 and ROS. Furthermore, VitD3 increased the baseline levels of antimicrobial peptide LL-37, which showed antiviral and immunoregulatory functions during in vitro DENV-2 infection of MDMs. Finally, we described that VitD3 can also regulate expression of some miRNAs that have been associated with inflammatory diseases. Overall, our results show two key messages. First, TLR2 has a key role in DENV-2 infection and immune response only in classical monocytes. Secondly, VitD3 and LL-37 have potential as therapeutic candidates as they show both antiviral and immunomodulatory effects against DENV-2 infection in human primary cells.
dc.descriptionTESIS CON DISTINCIÓN: Cum Laude (Meritoria)
dc.format208
dc.formatapplication/pdf
dc.formatapplication/pdf
dc.languageeng
dc.publisherInmunovirología
dc.publisherMedellín - Colombia
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rightshttp://purl.org/coar/access_right/c_abf2
dc.rightsDerechos reservados - Está prohibida la reproducción parcial o total de esta publicación
dc.subjectVirus del dengue
dc.subjectRespuesta inmune
dc.subjectVitamina D
dc.subjectMacrofagos
dc.subjectMonocitos
dc.subjectDengue virus
dc.subjectImmunity
dc.subjectMacrophages
dc.subjectMonocytes
dc.subjectVitamin D
dc.subjecthttps://id.nlm.nih.gov/mesh/D003716
dc.subjecthttps://id.nlm.nih.gov/mesh/D007109
dc.subjecthttps://id.nlm.nih.gov/mesh/D008264
dc.subjecthttps://id.nlm.nih.gov/mesh/D009000
dc.subjecthttps://id.nlm.nih.gov/mesh/D014807
dc.titleInnate immune response during DENV-2 infection of monocytes/macrophages
dc.typeinfo:eu-repo/semantics/doctoralThesis
dc.typeinfo:eu-repo/semantics/draft
dc.typehttp://purl.org/coar/resource_type/c_db06
dc.typehttps://purl.org/redcol/resource_type/TD
dc.typeTesis/Trabajo de grado - Monografía - Doctorado


Este ítem pertenece a la siguiente institución