Evaluación del papel inmunoregulador de sST2 en células mononucleares de sangre periférica durante la infección ex vivo con virus dengue

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dc.contributor.advisorCastellanos Parra, Jaime Eduardo
dc.contributor.advisorDelgado Tiria, Felix Giovanni
dc.contributor.authorPérez Acosta, Adriana Marisol
dc.date.accessioned2023-03-02T15:37:58Z
dc.date.available2023-03-02T15:37:58Z
dc.description.abstractEl dengue grave se caracteriza por altos niveles de citocinas como TNFα e IL-6, que pueden inducir aumento en la permeabilidad vascular, debido específicamente a un efecto pro-inflamatorio/vasodilatador sobre las células del endotelio vascular. Recientemente, se ha reportado que pacientes con dengue presentan niveles elevados de la isoforma soluble de ST2 (sST2) en el suero, sugiriendo que esta proteína podría jugar un papel importante durante la inmunopatogénesis de la enfermedad. Por otro lado, se ha reportado que sST2, un miembro de la familia de receptores de IL-1, inhibe la producción de citocinas proinflamatorias en macrófagos estimulados con lipopolisacárido (LPS). El presente trabajo tuvo como propósito establecer un modelo de infección in vitro, empleando células mononucleares de sangre periférica (CMSP) no fraccionadas infectadas con virus dengue serotipo 2 (DENV-2), que permitiera identificar la célula diana permisiva a la infección con el virus y aquellas células responsables de la producción de TNFα e IL-6, para así evaluar efecto de la proteína recombinante sST2-Fc sobre la producción de estas citocinas proinflamatorias. Como resultado, se encontró que las CMSP fueron permisivas a la infección y los monocitos CD14+, pero no linfocitos CD3+ o CD19+, fue la subpoblación celular preferencialmente infectada y responsable de la producción de TNFα e IL-6. Adicionalmente, las CMSP infectadas no produjeron sST2. Finalmente, la proteína recombinante sST2-Fc ejerció su efecto imunoregulador a una concentracion 10µg/mL sobre monocitos estimulados con LPS por 12 horas, pero este efecto no fue observado cuando los monocitos fueron infectados con DENV-2. Estos resultados podrían sugerir que la proteína sST2 no juega un papel en la regulación de la respuesta inmune durante la infección con DENV y que por el contrario, podría participar en el desarrollo del dengue grave.spa
dc.description.abstractenglishSevere dengue is characterized by high levels of cytokines such as TNFα and IL-6, which can induce increased vascular permeability, specifically due to a pro-inflammatory/vasodilator effect on vascular endothelial cells. Recently, it has been reported that patients with dengue present elevated levels of the soluble isoform of ST2 (sST2) in serum, suggesting that this protein could play an important role during the immunopathogenesis of the disease. On the other hand, it has been reported that sST2, a member of the IL-1 receptor family, inhibits the production of proinflammatory cytokines in lipopolysaccharide (LPS)-stimulated macrophages. The present work had the purpose of establishing an in vitro infection model, using unfractionated peripheral blood mononuclear cells (PBMC) infected with dengue virus serotype 2 (DENV-2), that would allow the identification of the target cell permissive to infection with the virus and those cells responsible for the production of TNFα and IL-6, in order to evaluate the effect of the recombinant protein sST2-Fc on the production of these proinflammatory cytokines. As a result, it was found that PBSCs were permissive to infection and CD14+ monocytes, but not CD3+ or CD19+ lymphocytes, was the cell subpopulation preferentially infected and responsible for TNFα and IL-6 production. Additionally, infected PBSCs did not produce sST2. Finally, the recombinant sST2-Fc protein exerted its imunoregulatory effect at a concentration of 10µg/mL on monocytes stimulated with LPS for 12 hours, but this effect was not observed when monocytes were infected with DENV-2. These results may suggest that the sST2 protein does not play a role in the regulation of the immune response during DENV infection and, on the contrary, may be involved in the development of severe dengue.eng
dc.description.degreelevelMaestríaspa
dc.description.degreenameMagíster en Ciencias Básicas Biomédicasspa
dc.format.mimetypeapplication/pdf
dc.identifier.instnameinstname:Universidad El Bosquespa
dc.identifier.reponamereponame:Repositorio Institucional Universidad El Bosquespa
dc.identifier.repourlrepourl:https://repositorio.unbosque.edu.co
dc.identifier.urihttps://hdl.handle.net/20.500.12495/10093
dc.language.isospa
dc.publisher.facultyFacultad de Medicinaspa
dc.publisher.grantorUniversidad El Bosquespa
dc.publisher.programMaestría en Ciencias Básicas Biomédicasspa
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dc.rights.accessrightshttps://purl.org/coar/access_right/c_14cb
dc.rights.localAcceso cerradospa
dc.subject.nlmW 50
dc.titleEvaluación del papel inmunoregulador de sST2 en células mononucleares de sangre periférica durante la infección ex vivo con virus denguespa
dc.title.translatedEvaluation of the immunoregulatory role of sST2 in peripheral blood mononuclear cells during ex vivo dengue virus infection
dc.type.coarhttps://purl.org/coar/resource_type/c_bdcc
dc.type.coarversionhttps://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.driverinfo:eu-repo/semantics/masterThesis
dc.type.hasversioninfo:eu-repo/semantics/acceptedVersion
dc.type.localTesis/Trabajo de grado - Monografía - Maestríaspa

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Maestría en Ciencias Básicas Biomédicas