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| Author(s): |
Daniel Augusto de Toledo Teixeira
Total Authors: 1
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| Document type: | Master's Dissertation |
| Press: | Campinas, SP. |
| Institution: | Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia |
| Defense date: | 2019-04-12 |
| Examining board members: |
José Luiz Proença Módena;
Eurico de Arruda Neto;
Alessandro dos Santos Farias
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| Advisor: | José Luiz Proença Módena |
| Abstract | |
Diseases caused by emerging arboviruses has had a great impact on public health, particularly in the last 30 years. The recent Zika virus (ZIKV) epidemic in Brazil and the Oropouche orthobunyavirus (OROV) outbreaks in the Amazon region exemplify the impact of arboviruses on a susceptible population. The disease caused by OROV has a febrile rash character called Oropouche fever, and it may progress to neurological complications in part of symptomatic patients. However, the pathogenetic details and roles of adaptive immunity in the protection from virus infection and development of neurological complications are not yet fully elucidated. Thus, the objective of this dissertation was to evaluate the role of adaptive immune response, highlighting the role of B and T cells, for neuroinvasion control and pathogenesis by OROV. We demonstrated that mice without mature B and T lymphocytes (Rag1-/-) are vulnerable to viral infection age-independently, as well as mice without only mature B lymphocytes (µMT). On the other hand, wild-type (WT) and lacking only mature T lymphocyte (TCRbd) mice were resistant. The presence of neutralizing virus-specific antibodies produced by WT mice was essential for disease control in Rag1-/- when transferred within three days of infection, and WT mice sera harvested at 6 days post OROV infection was also able to protect Rag1-/-. Furthermore, our ex vivo infections demonstrated that B lymphocytes can contribute to innate response by type I interferon production and viral recognition by pattern recognition receptors. Therefore, our results demonstrate that B cells have a central protection role against OROV in murine model by neutralizing antibody production that could prevent reinfections and late clinical manifestations, and by its involvement during initial events such as innate response and antibody production, both T lymphocytes independently. (AU) | |
| FAPESP's process: | 17/02402-0 - The role of adaptive immune response in neuroinvasion by Oropouche and Zika virus |
| Grantee: | Daniel Augusto de Toledo Teixeira |
| Support Opportunities: | Scholarships in Brazil - Master |