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Estudos do efeito da proteína recombinante Akirin na infeção por Plasmodium berghei em Anopheles gambiae s.s.
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A malária é considerada uma das doenças mais importantes transmitida pelos mosquitos, tendo um grande impacto nos países não desenvolvidos. O controlo da malária continua fortemente dependente do uso de fármacos e estratégias para controlo do vetor. Como muitos compostos anti-maláricos já não são eficazes, novas estratégias de controlo são urgentemente necessárias, especialmente devido também ao facto de existirem poucos fármacos disponíveis e não existirem vacinas aprovadas. As proteínas akirin constituem um grupo recentemente renomeado de proteínas conservadas em insetos e vertebrados. O gene akirin atua em paralelo com o fator de transcrição NF-kB, a jusante na via Imd, tendo uma forte atividade anti-plasmódio. O ortólogo da akirin nas carraças, subolesin, tem-se revelado como um antigénio protetor contra carraças em Ixodes scapularis. Estudos recentes mostraram uma redução na sobrevivência e/ou fertilidade destes vetores, após a alimentação em hospedeiros imunizados com os antigénios akirin e subolesin.
Nos nossos ensaios, foi realizado o silenciamento do gene akirin por RNAi em Anopheles gambiae s.s.. Os resultados obtidos mostram uma diminuição na produção de ovos de 39%, um aumento da intensidade de infeção de 35% e uma diminuição da sobrevivência de 17%.
Estes resultados fortalecem dados anteriores relativos à importância do gene akirin no sistema imune, sugerindo também o seu papel na reprodução. Os nossos dados reforçam a hipótese de que a akirin pode constituir um potencial antigénio protetor para o controlo do mosquito.
Experiências sobre a alimentação natural de An. gambiae s.s. em murganhos imunizados com akirin foram realizados em paralelo mas os resultados obtidos não mostraram proteção contra a infeção por Plasmodium sp..
Malaria is considered one of the most important diseases transmitted by mosquito, having a great impact on underdeveloped countries. Malaria control is still heavily dependent of the use of drugs and vector control strategies. As many anti-malarial compounds are no longer effective, new control approaches are urgently needed, especially due too the fact that are few drugs available and no approved vaccines. Akirins constitute a recently renamed group of evolutionarily conserved proteins in insects and vertebrates. The gene akirin acts in parallel with the NF-kB transcription factor downstream of the Imd pathway having a potent anti-Plasmodium activity. Subolesin, the ortholog of akirin in ticks, was revealed as a tick protective antigen in Ixodes scapularis. Recent studies showed a reduction in the survival and/or fertility of these vectors after feeding in hosts immunized with subolesin and akirin antigens. In our experiments, akirin gene knockdown by RNAi in Anopheles gambiae s.s. were carried on. Results obtained showed a decrease in eggs production of 39%, an increased infection intensity of 35% and a decrease on survival of 17%. Together, these results strengthen previous data concerning the importance of akirin gene in the immunity system, suggesting as well its role on the reproduction. Our data reinforce that akirin may constitute a potential protective antigen for the control of mosquito. Experiments regarding An.gambiae s.s. mosquitoes natural feeding on mice immunized with akirin were as well developed but the results obtained didn’t show any protection against Plasmodium sp. infection.
Malaria is considered one of the most important diseases transmitted by mosquito, having a great impact on underdeveloped countries. Malaria control is still heavily dependent of the use of drugs and vector control strategies. As many anti-malarial compounds are no longer effective, new control approaches are urgently needed, especially due too the fact that are few drugs available and no approved vaccines. Akirins constitute a recently renamed group of evolutionarily conserved proteins in insects and vertebrates. The gene akirin acts in parallel with the NF-kB transcription factor downstream of the Imd pathway having a potent anti-Plasmodium activity. Subolesin, the ortholog of akirin in ticks, was revealed as a tick protective antigen in Ixodes scapularis. Recent studies showed a reduction in the survival and/or fertility of these vectors after feeding in hosts immunized with subolesin and akirin antigens. In our experiments, akirin gene knockdown by RNAi in Anopheles gambiae s.s. were carried on. Results obtained showed a decrease in eggs production of 39%, an increased infection intensity of 35% and a decrease on survival of 17%. Together, these results strengthen previous data concerning the importance of akirin gene in the immunity system, suggesting as well its role on the reproduction. Our data reinforce that akirin may constitute a potential protective antigen for the control of mosquito. Experiments regarding An.gambiae s.s. mosquitoes natural feeding on mice immunized with akirin were as well developed but the results obtained didn’t show any protection against Plasmodium sp. infection.
Descrição
Palavras-chave
Parasitologia médica Malária Anopheles gambiae Akirin Antigénio protetor Plasmodium Silenciamento
Contexto Educativo
Citação
Editora
Instituto de Higiene e Medicina Tropical