Priming events and development of tolerance upon influenza A virus and Staphylococcus aureus infection

• Autor(a) principal: Ferreira, Diogo Filipe Rocha
• 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
• topic: Staphylococcus aureus; Influenza; Coinfeção

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