Priming events and development of tolerance upon influenza A virus and Staphylococcus aureus infection
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Tipo de documento: | Dissertação |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10773/25175 |
Resumo: | Influenza viruses (IV) cause infections of the upper and lower respiratory tract and they are the causative agent of the flu, which causes several thousand hospitalizations and deaths each year, due complications that turn IV infections into more serious diseases, like secondary bacterial infections. Staphylococcus aureus (S. aureus) infections occur during and/or shortly after recovery from influenza and they are associated with increased morbidity and mortality. The disease outcome is due to deregulated immune response associated with increased cytokine and chemokine expression, enhanced pathogen load and tissue lesions. This process is regulated by complex and highly dynamic interaction between bacteria, virus, and the host organism. Although some of the mechanisms leading to secondary bacterial infections are known, the knowledge on how primary bacterial exposure will affect the course of a secondary viral infection is still limited. For this reason, it is important to understand the underlying mechanisms of how this type of co-infections develop. Then, infections models were established in order to mimic a primary bacterial exposure, followed by a secondary viral infection and the outcomes were analyzed. For that, techniques like Western-bloting and qRT-PCR, were performed in order to determine the protein and mRNA synthesis of viral, bacterial and host structural and signaling pathways protein elements. Cell morphology was also evaluated to determine the success and extention of viral and or bacterial infections. Besides that, pathogen loads were also quantified and analyzed. Results show that, a primary bacterial infection primes the host cells towards post viral infection and that the outcome is worse than compared to single infections. Tissue damage is higher, pathogen loads increase, immune response is exacerbated and anti-viral mechanisms, like the type I IFN response is blocked, by inhibition of STAT1-STAT2 dimerization. With this, there is evidence that a bacterial infection, primes the host cells for a secondary viral infection |
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Priming events and development of tolerance upon influenza A virus and Staphylococcus aureus infectionStaphylococcus aureusInfluenzaCoinfeçãoInfluenza viruses (IV) cause infections of the upper and lower respiratory tract and they are the causative agent of the flu, which causes several thousand hospitalizations and deaths each year, due complications that turn IV infections into more serious diseases, like secondary bacterial infections. Staphylococcus aureus (S. aureus) infections occur during and/or shortly after recovery from influenza and they are associated with increased morbidity and mortality. The disease outcome is due to deregulated immune response associated with increased cytokine and chemokine expression, enhanced pathogen load and tissue lesions. This process is regulated by complex and highly dynamic interaction between bacteria, virus, and the host organism. Although some of the mechanisms leading to secondary bacterial infections are known, the knowledge on how primary bacterial exposure will affect the course of a secondary viral infection is still limited. For this reason, it is important to understand the underlying mechanisms of how this type of co-infections develop. Then, infections models were established in order to mimic a primary bacterial exposure, followed by a secondary viral infection and the outcomes were analyzed. For that, techniques like Western-bloting and qRT-PCR, were performed in order to determine the protein and mRNA synthesis of viral, bacterial and host structural and signaling pathways protein elements. Cell morphology was also evaluated to determine the success and extention of viral and or bacterial infections. Besides that, pathogen loads were also quantified and analyzed. Results show that, a primary bacterial infection primes the host cells towards post viral infection and that the outcome is worse than compared to single infections. Tissue damage is higher, pathogen loads increase, immune response is exacerbated and anti-viral mechanisms, like the type I IFN response is blocked, by inhibition of STAT1-STAT2 dimerization. With this, there is evidence that a bacterial infection, primes the host cells for a secondary viral infectionuma infeção respiratória aguda, de curta duração e é responsável por milhares de hospitalizações e mortes anuais, principalmente, devido a complicações que transformam infeções pelo vírus influenza em doenças mais graves, como infeções bacterianas secundárias. As infeções por Staphylococcus aureus (S. aureus) ocorrem durante, ou logo após a recuperação da infeção por influenza e estão associadas a maior morbidade e mortalidade. O resultado da doença é devido à resposta imune desregulada, associada ao aumento da expressão de citocinas e quimiocinas, aumento da carga de patogénicos e de lesões no tecido pulmonar. Este processo é regulado pela interação complexa e altamente dinâmica entre bactérias, vírus e o organismo hospedeiro. Embora alguns dos mecanismos causadores de infeções bacterianas secundárias sejam já conhecidos, o modo como uma exposição bacteriana primária afeta o desenvolver de uma infeção viral secundária ainda é limitado. Por essa razão, é importante entender os mecanismos subjacentes de como esse tipo de coinfecção se desenvolve. Modelos de infeção foram estabelecidos para reproduzir uma exposição bacteriana primária, seguida de uma infeção viral secundária, e assim, os resultados finais foram analisados. Para isso, várias técnicas, como Western-bloting e qRT-PCR, foram utilizadas de modo a avaliar a síntese proteica e de mRNAs, de elementos virais, bacterianos ou do hospedeiro, tais como, proteínas estruturais e ainda elementos de vias de sinalização. A morfologia celular foi outro parâmetro avaliado para determinar o sucesso e a extensão das infeções virais e, ou, bacterianas. Além disso, a quantificação da carga microbiana e viral foram também analisados. Estes mostram que, uma infeção bacteriana primária estimula as células hospedeiras para uma infeção secundária viral e que o desfecho desta, é pior do que em comparação com infeções com apenas cada um dos patogénicos. O dano é maior, as quantidades de agentes patogénicos aumentam, a resposta imune é maior e desregulada e mecanismos antivirais, como a resposta do IFN tipo I, são bloqueados, neste caso pela inibição da dimerização de STAT1-STAT2, pela bactéria. Concluindo, estes resultados mostram evidências de que uma infeção bacteriana estimula as células hospedeiras para uma infeção viral secundária2018-12-112018-12-11T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10773/25175TID:202233650engFerreira, Diogo Filipe Rochainfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-02-22T11:49:03Zoai:ria.ua.pt:10773/25175Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T02:58:34.410922Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Priming events and development of tolerance upon influenza A virus and Staphylococcus aureus infection |
title |
Priming events and development of tolerance upon influenza A virus and Staphylococcus aureus infection |
spellingShingle |
Priming events and development of tolerance upon influenza A virus and Staphylococcus aureus infection Ferreira, Diogo Filipe Rocha Staphylococcus aureus Influenza Coinfeção |
title_short |
Priming events and development of tolerance upon influenza A virus and Staphylococcus aureus infection |
title_full |
Priming events and development of tolerance upon influenza A virus and Staphylococcus aureus infection |
title_fullStr |
Priming events and development of tolerance upon influenza A virus and Staphylococcus aureus infection |
title_full_unstemmed |
Priming events and development of tolerance upon influenza A virus and Staphylococcus aureus infection |
title_sort |
Priming events and development of tolerance upon influenza A virus and Staphylococcus aureus infection |
author |
Ferreira, Diogo Filipe Rocha |
author_facet |
Ferreira, Diogo Filipe Rocha |
author_role |
author |
dc.contributor.author.fl_str_mv |
Ferreira, Diogo Filipe Rocha |
dc.subject.por.fl_str_mv |
Staphylococcus aureus Influenza Coinfeção |
topic |
Staphylococcus aureus Influenza Coinfeção |
description |
Influenza viruses (IV) cause infections of the upper and lower respiratory tract and they are the causative agent of the flu, which causes several thousand hospitalizations and deaths each year, due complications that turn IV infections into more serious diseases, like secondary bacterial infections. Staphylococcus aureus (S. aureus) infections occur during and/or shortly after recovery from influenza and they are associated with increased morbidity and mortality. The disease outcome is due to deregulated immune response associated with increased cytokine and chemokine expression, enhanced pathogen load and tissue lesions. This process is regulated by complex and highly dynamic interaction between bacteria, virus, and the host organism. Although some of the mechanisms leading to secondary bacterial infections are known, the knowledge on how primary bacterial exposure will affect the course of a secondary viral infection is still limited. For this reason, it is important to understand the underlying mechanisms of how this type of co-infections develop. Then, infections models were established in order to mimic a primary bacterial exposure, followed by a secondary viral infection and the outcomes were analyzed. For that, techniques like Western-bloting and qRT-PCR, were performed in order to determine the protein and mRNA synthesis of viral, bacterial and host structural and signaling pathways protein elements. Cell morphology was also evaluated to determine the success and extention of viral and or bacterial infections. Besides that, pathogen loads were also quantified and analyzed. Results show that, a primary bacterial infection primes the host cells towards post viral infection and that the outcome is worse than compared to single infections. Tissue damage is higher, pathogen loads increase, immune response is exacerbated and anti-viral mechanisms, like the type I IFN response is blocked, by inhibition of STAT1-STAT2 dimerization. With this, there is evidence that a bacterial infection, primes the host cells for a secondary viral infection |
publishDate |
2018 |
dc.date.none.fl_str_mv |
2018-12-11 2018-12-11T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10773/25175 TID:202233650 |
url |
http://hdl.handle.net/10773/25175 |
identifier_str_mv |
TID:202233650 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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