Estudo do efeito imunomodulador de vesículas isoladas durante a infecção por trypanosoma cruzi na célula hospedeira

• Ano de defesa: 2018
• Autor(a) principal: Andrade, Andre Cronemberger [UNIFESP]
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de São Paulo (UNIFESP)
• Palavras-chave em Português: Extracellular vesicles; Macrophage; Infection; Vesículas extracelulares; Trypanosoma cruzi; Macrófagos; Infecção
• Link de acesso: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=6456735; https://repositorio.unifesp.br/handle/11600/53166

The extracellular vesicles shed by trypomastigote forms of Trypanosoma cruzi have the ability to interact, increase tissue invasion and modulate the host innate response via TLR2. In T. cruzi infection, induction of the Th1-type response is crucial for promoting protection against the parasite. The aim of the study was to investigate the role of these vesicles as immunomodulatory agents that act during the initial phase of host immune response. THP-1 cells were differentiated into macrophages and infected with T. cruzi. Infected cell culture supernatants of macrophages were collected by ultracentrifugation at different times after infection and the released material was analyzed by NTA. Increased numbers of EVs ranging from 50 to 300 nm were found in the macrophages supernatant 24 hours post infection. Large number of EV from infected compared to non-infected macrophages was observed by scanning electron microscopy. Released EVs contained CD63, CD9, and MHC class II revealing their exosomal and macrophagic origin. No parasite antigens were detected. In addition, the ability of these EVs to translocate NF-kB by TLR2 receptors was evidenced. As a consequence of this interaction, the expression of these receptors is increased. EVs were also able to stimulate the production of proinflammatory cytokines (TNF-α, IL-6 and IL-1β). In this way we observed the potential of EVs derived from T. cruzi infection in the maintenance of the inflammatory response and increase the number of parasites and infected cells in the host.