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Estudo do papel da imunidade inata nas infeções por micobactérias
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Authors
Advisor(s)
Abstract(s)
[PT] Desde os primórdios da humanidade que existem relatos de infecções
respiratórias causadas por micobactérias. A incidência de infecções por Micobactérias
Não-Tuberculosas (MNT), consideradas oportunistas, tem aumentado gradualmente
atingindo sobretudo a população imunodeprimida.
As MNTs são maioritariamente ambientais e ubíquas. Sendo o difícil
diagnóstico, a resistência aos antibióticos e o escasso conhecimento da
patogenicidade destas micobactérias, os principais impulsores do seu estudo.
Os macrófagos alveolares, em infecções do sistema respiratório, são as
primeiras células do sistema imunitário que contactam com as MNTs. Estes irão
desencadear de imediato uma resposta imunitária inata.
Este trabalho teve como principal objectivo avaliar a resposta imunitária
durante uma infecção com MNTs utilizando células THP-1 como modelo de
macrófagos alveolares humanos. Para tal, foi avaliada a sobrevivência de algumas
MNTs no interior dos macrófagos, seguida do estudo de vários componentes da
resposta imunitária: maturação do fagossoma; produção de molécula pró-
inflamatórias; e indução da morte celular.
Foi possível observar a existência de 3 perfis de persistência intracelular: M.
smegmatis é eliminado; M. fortuitum ATCC6841 apresenta um perfil de latência; o M.
fortuitum 747/08, M. abscessus 549/08, M. avium ATCC25291 e M.avium 60/08
apresentam um perfil de crescimento. A maturação dos fagossomas de MNT é
bloqueada duma forma menos eficiente do que a dos fagossomas de M. tuberculosis.
Apenas o M. avium 60/08 foi capaz de induzir a produção de NO e IL-10. E ainda que
existe a indução da apoptose diferenciada entre as estirpes estudadas, sendo o M.
avium 60/08 o melhor indutor.
[ENG] Mycobacteria respiratory infections are described since the dawn of humanity. Non-tuberculous Mycobacteria (NTM) infections have been gradually increasing, being regarded as opportunistic this mycobacteria affect mostly immunocompromised individuals. The majority of NTMs are environmental and ubiquitous. A difficult diagnosis, antibiotic resistance and the lack of knowledge about pathogenesis of these mycobacteria, are the main impellers of their study. The alveolar macrophages, in respiratory system infections, are the first immune system cells to contact with the NTM triggering the innate immune response. This work aimed to evaluate the immune response during NTM infection using THP-1 cells as a model of human alveolar macrophages. The survival of several NTMs within macrophages was evaluated. The role played by different immune response mechanisms such as phagosome maturation, production of inflammatory mediators and induction of cell death in NTM fate was also evaluated. Three different intracellular persistence profiles were observed. M. smegmatis was cleared; M. fortuitum ATCC6841 presented a profile of latency; M. fortuitum 747/08, M. abscessus 549/08, M. avium ATCC25291 and M.avium 60/08 were able to replicate. It was found that maturation block for NTM phagosome was less efficient than M.tuberculosis. Only M. avium 60/08 was able to trigger NO and IL-10 production. It was also found that there is induction of apoptosis among the studied strains, being h M. avium 60/08 the best inducer.
[ENG] Mycobacteria respiratory infections are described since the dawn of humanity. Non-tuberculous Mycobacteria (NTM) infections have been gradually increasing, being regarded as opportunistic this mycobacteria affect mostly immunocompromised individuals. The majority of NTMs are environmental and ubiquitous. A difficult diagnosis, antibiotic resistance and the lack of knowledge about pathogenesis of these mycobacteria, are the main impellers of their study. The alveolar macrophages, in respiratory system infections, are the first immune system cells to contact with the NTM triggering the innate immune response. This work aimed to evaluate the immune response during NTM infection using THP-1 cells as a model of human alveolar macrophages. The survival of several NTMs within macrophages was evaluated. The role played by different immune response mechanisms such as phagosome maturation, production of inflammatory mediators and induction of cell death in NTM fate was also evaluated. Three different intracellular persistence profiles were observed. M. smegmatis was cleared; M. fortuitum ATCC6841 presented a profile of latency; M. fortuitum 747/08, M. abscessus 549/08, M. avium ATCC25291 and M.avium 60/08 were able to replicate. It was found that maturation block for NTM phagosome was less efficient than M.tuberculosis. Only M. avium 60/08 was able to trigger NO and IL-10 production. It was also found that there is induction of apoptosis among the studied strains, being h M. avium 60/08 the best inducer.
Description
Dissertação de mestrado em Biologia (Biologia Molecular e Genética, apresentada à Faculdade de Ciências da Universidade de Lisboa, 2014
Luísa Jordão, investigadora do Departamento de Doenças Infeciosas do INSA
Luísa Jordão, investigadora do Departamento de Doenças Infeciosas do INSA
Keywords
Micobactérias não Tuberculosas (MNT) Interação Micobactéria-hospedeiro Resposta Imunitária Inata Morte Celular Infecções Respiratórias Non-Tuberculous Mycobacteria Mycobacteria-host Interactions Innate Imune Response Celular Death