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The reciprocal influence of malaria and sleeping sickness co-infections

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Resumo:Malaria and sleeping sickness are tropical diseases that share overlapping spacial distributions in sub-Saharan Africa. Malaria is caused by several Plasmodium species, while sleeping sickness is caused by Trypanosoma brucei. Co-infections between these two eukaryotic parasites are likely to happen in humans, but this problem remains largely understudied. In this thesis, we tested whether an ongoing infection by one parasite would influence progression of a secondary infection by the other. The type of co-infection characterized most thoroughly throughout this thesis was the one in which mice were primarily infected by T. brucei and submitted to a secondary infection by P. berghei. In this case, we observed a dramatic impairment of the liver infection by the latter parasite. Immunofluorescence microscopy analysis and qRT-PCR revealed that a primary T. brucei infection is able to reduce approximately 80% P. berghei liver infection in the first 6 hours of its development, which means that elimination of Plasmodium parasites or Plasmodium-infected hepatocytes occurs very early. Several experiments were performed to address the mechanism of this T. brucei induced impairment of a P. berghei liver infection. Our results suggest that Plasmodium elimination may be immune response-dependent and indicate the involvement of pro-inflammatory cytokines, such as IFN-γ. The upregulation of this cytokine in co-infected mice leads to a production of TNF-α and nitric oxide, which may eliminate Plasmodium parasites. Interestingly, we observed that mice co-infected with T. brucei and P. berghei did not develop experimental cerebral malaria, neither when Plasmodium infection went through a liver stage or directly from infected blood. This work revealed hitherto unknown features of a Trypanosoma/Plasmodium co-infection and paved the way to a potential application in the control of malaria infections.
Autores principais:Vaz, Ana Margarida Roque Sanches
Assunto:Malária Doença do sono Plasmodium Trypanosoma Teses de mestrado - 2013
Ano:2013
País:Portugal
Tipo de documento:dissertação de mestrado
Tipo de acesso:acesso restrito
Instituição associada:Universidade de Lisboa
Idioma:inglês
Origem:Repositório da Universidade de Lisboa

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