| dc.contributor | Kalergis-Parra, Alexis | |
| dc.contributor | Pontificia Universidad Católica de Chile | |
| dc.creator | González-Muñoz, Pablo Alberto | |
| dc.date | 2017-03-23T13:12:56Z | |
| dc.date | 2022-08-18T22:00:20Z | |
| dc.date | 2017-03-23T13:12:56Z | |
| dc.date | 2022-08-18T22:00:20Z | |
| dc.date | 2008 | |
| dc.date.accessioned | 2023-08-21T20:30:19Z | |
| dc.date.available | 2023-08-21T20:30:19Z | |
| dc.identifier | http://creativecommons.org/licenses/by-nc-nd/3.0/cl/ | |
| dc.identifier | https://hdl.handle.net/10533/171810 | |
| dc.identifier.uri | https://repositorioslatinoamericanos.uchile.cl/handle/2250/8278609 | |
| dc.description | Respiratory syncytial virus (RSV) infection is one of the leading causes of infant
hospitalization and a major health and economic burden worldwide. Infection with this
virus induces an exacerbated innate pro-inflammatory immune response characterized by
abundant immune ccli inflitration into the airways and lung tissue damage. RSV also
impairs the induction of an adequate adaptive T ccii imniune response, which favors virus
pathogenesis. Unfortunately, to date there are no efficient vaccines against this virus.
Recent in vi/ro and in vivo studies suggest that RSV infection can prevent T ccli activation,
a phenomcnon attributed in part to cytokines and chernokines secreted by RSV-infected
celis. Efficient immunity against viruses is pronioted by dendritic ceils (DCs), professional
antigen presenting celis, that prime antigen-specific helper and cytotoxic T celis. Therefore,
it would he to the advantage of RSV to impair DC function and prevent the induction of T
cdl irnmunity. In this thesis it is shown that, aithough RSV infection induces maturation of
murine DCs, these ccils are rendered unable to activate antigen-spccific T cells. Inhibition
of T ccli activation by RSV was observed independently of the type of TCR-ligand on the
DC surface and applied to cognate-, alio- and super-antigen stimulation. As a result of
exposure to RSV-infected DCs. T ceils became unresponsive to subsequent TCR
engagement. RSV-mediated impairrnent in T cdl activation required DC-T ccli contact and
involved inhihition of imrnunoiogical synapse assembiy between these celis. Our data
suggcst that impairment of immunoiogical synapse could contrihute to RSV pathogenesis
by evading adaptive irnmunity and reducing T celi-mediated virus clearance. Further, we
evaluated in a mouse model for RSV infection whcthcr prcvious imrnunization with an
attenuated strain of Sa/inane/la Typhimurium, expressing the RSV-M2 antigen couid protect mice upon challenge with the virus. 1-lowever, mice immunized with this
recombinant strain displayed pathogenesis symptoms similar to unimmunized mice afler
virus challenge. Neverthe!ess, failure to induce protection by this recombinant strain was
attributed to the induction of poor irnmunity against the RSV-M2 protein. The reasons
underlying these observations are discussed. | |
| dc.description | PFCHA-Becas | |
| dc.description | Doctor en Ciencias Biológicas, Mención Genética Molecular Y Microbiología | |
| dc.description | 166 | |
| dc.description | PFCHA-Becas | |
| dc.description | TERMINADA | |
| dc.format | application/pdf | |
| dc.language | spa | |
| dc.language | eng | |
| dc.relation | instname: Conicyt | |
| dc.relation | reponame: Repositorio Digital RI2.0 | |
| dc.relation | instname: Conicyt | |
| dc.relation | reponame: Repositorio Digital RI2.0 | |
| dc.relation | info:eu-repo/grantAgreement/PFCHA-Becas/RI20 | |
| dc.relation | info:eu-repo/semantics/dataset/hdl.handle.net/10533/93488 | |
| dc.rights | Atribución-NoComercial-SinDerivadas 3.0 Chile | |
| dc.rights | info:eu-repo/semantics/openAccess | |
| dc.title | Identificación de los mecanismos moleculares desarrollados por el virus respiratorió sincicial para evadir la respuesta inmune adquirida y generación de cepas bacterianas recombinantes inductoras de inmunidad anti-viral. | |
| dc.type | Tesis Doctorado | |
| dc.type | info:eu-repo/semantics/doctoralThesis | |
| dc.type | info:eu-repo/semantics/publishedVersion | |
| dc.type | Tesis | |
| dc.coverage | Santiago | |
