Publicação
The importance of apoptosis of Plasmodium-infected cells in the generation of immunity against malaria infection
| Resumo: | Despite the efforts towards eradication, malaria remains the most deadly parasitic and vector-borne disease, urging for the development of an effective antimalarial vaccine. Recently, a renewed interest in Plasmodium attenuated whole-organism vaccine strategies has emerged, long acknowledged to experimentally induce full and sterile immunity against malaria in mice, monkeys and humans. This approach involves the use of non-replicating but metabolic active sporozoites, either attenuated by exposition to radiation, the Radiation-Attenuated Sporozoites (RAS), or by genetic modification, the Genetically-Attenuated Sporozoites (GAS). These attenuated parasites are able to infect hepatocytes in vivo as normal sporozoites, but are unable to fully develop in the liver. This arrest in development has been associated with their apparent failure to prevent host cell apoptosis, which leads to the formation of apoptotic bodies filled with parasite antigens. Several pieces of evidence have suggested that these apoptotic bodies may provide an optimal source of antigens for dendritic cells cross-presentation, and therefore, immune response activation. The aim of this project was to assess whether apoptosis of RAS or GAS infected hepatocytes is involved in the induced protective immunity response against subsequent parasite challenges. Results obtained through the immunization of C57BL/6 background caspase-3 deficient mice with P. berghei RAS or p36p- GAS revealed that these mice are only partially protected against further infection. These suggest that at least to some extent, caspase-3 mediated apoptosis of infected hepatocytes may be important in generation of immunity by attenuated parasites. |
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| Autores principais: | Marques, Catarina de Almeida, 1987- |
| Assunto: | Biologia molecular Malária Parasitas Plasmodium Teses de mestrado - 2010 |
| Ano: | 2010 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório da Universidade de Lisboa |
| Resumo: | Despite the efforts towards eradication, malaria remains the most deadly parasitic and vector-borne disease, urging for the development of an effective antimalarial vaccine. Recently, a renewed interest in Plasmodium attenuated whole-organism vaccine strategies has emerged, long acknowledged to experimentally induce full and sterile immunity against malaria in mice, monkeys and humans. This approach involves the use of non-replicating but metabolic active sporozoites, either attenuated by exposition to radiation, the Radiation-Attenuated Sporozoites (RAS), or by genetic modification, the Genetically-Attenuated Sporozoites (GAS). These attenuated parasites are able to infect hepatocytes in vivo as normal sporozoites, but are unable to fully develop in the liver. This arrest in development has been associated with their apparent failure to prevent host cell apoptosis, which leads to the formation of apoptotic bodies filled with parasite antigens. Several pieces of evidence have suggested that these apoptotic bodies may provide an optimal source of antigens for dendritic cells cross-presentation, and therefore, immune response activation. The aim of this project was to assess whether apoptosis of RAS or GAS infected hepatocytes is involved in the induced protective immunity response against subsequent parasite challenges. Results obtained through the immunization of C57BL/6 background caspase-3 deficient mice with P. berghei RAS or p36p- GAS revealed that these mice are only partially protected against further infection. These suggest that at least to some extent, caspase-3 mediated apoptosis of infected hepatocytes may be important in generation of immunity by attenuated parasites. |
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