Avalia??o do efeito do lipofosfoglicano (LPG) de Leishmania amazonensis e de Leishmania braziliensis na infec??o por Leishmania

Na busca por novos medicamentos e formas de tratamento da Leishmaniose estudos t?m sido direcionados ? compreens?o dos mecanismos de intera??o parasito/hospedeiro. A resposta inicial desencadeada pelo parasito parece ser crucial no direcionamento da infec??o e no processo de cura ou resist?ncia. A mol?cula de LPG, presente na superf?cie das formas promastigotas de protozo?rios do g?nero Leishmania, por possuir grande variabilidade estrutural interespec?fica tem se tornado objeto de estudo a fim de se elucidar mecanismos iniciais desta importante intera??o. Neste trabalho foram verificadas grandes diferen?as na propor??o da mol?cula de LPG de L. braziliensis e de L. amazonensis evidenciando a diversidade estrutural e/ou quantitativa deste glicol?pide de superf?cie. Verificamos que a administra??o LPG de L. braziliensis e o LPG de L. amazonensis, em excesso, durante infec??es por L. braziliensis, no modelo murino n?o foram capazes de alterar o perfil de les?o provocado pelo protozo?rio. No entanto c?lulas do ba?o e linfonodo de camundongos infectados com L. baziliensis na presen?a de LPG foram capazes de produzir a citocina IL-10, relacionada aos mecanismos de regula??o da resposta imune celular. Al?m disto, LPGs purificados n?o foram capazes de ativar macr?fagos intraperitoneais, por?m, quando adicionados em conjunto com LPS e IFN-? foram capazes de alterar o perfil de ativa??o quanto a produ??o de NO ou IL-10. O LPG de L. braziliensis tem efeito direto em macr?fagos ativados diminuindo a produ??o de NO de maneira dose dependente, demonstrando efeito direto deste LPG na elimina??o do protozo?rio pela c?lula hospedeira. No entanto, o LPG de L. amazonensis n?o induz tal efeito, por?m, ? capaz de diminuir a produ??o de IL-10. Receptores do Tipo Toll 2 (TLR2) parecem n?o estar envolvidos nestes processos. Apesar destas altera??es provocadas pelos LPGs estudados tais mol?culas n?o foram capazes de modificar a express?o, em macr?fagos, de mol?culas envolvidas na ativa??o, apresenta??o e migra??o celular. Nossos dados demonstram que a presen?a do LPG ? capaz de induzir diferentes mecanismos da resposta imune durante a ativa??o de macr?fagos, tal fato pode ocorrer devido ? variabilidade da mol?cula entre as esp?cies de Leishmania. Este trabalho vem contribuir para elucida??o de mecanismos complexos que envolvem a diversidade da resposta imune do hospedeiro e consequentemente a cura ou resist?ncia a infec??es por parasitos do g?nero Leishmania.The search for new drugs for the treatment of Leishmaniasis has focused in the understanding of the mechanisms in host-parasite interaction. This disease manifests itself in a wide array of manifestations due to both parasite- and host-related peculiarities. The early immune response caused by the parasite can be crucial in the development of infection and in the healing and/or resistance process. The Lipophospohglycan (LPG) molecule, present in large amounts in the surface of promastigotes forms, has shown great structural variability amongst the several species that belong to the Leishmania genus. Therefore, understanding the initial mechanisms of the interaction of LPG in the host- parasite relationship is an important step towards understanding the differences between the several presentations of this disease. In this work differences were verified in the proportion of the molecule of LPG in L. braziliensis and L. amazonensis evidencing the diversity structural and/or quantitative of this surface glycoconjugate. Despite the variability between LPGs, their inoculation in association with L. braziliensis in infections in mice were not capable to alter the lesion development provoked by the protozoan. However spleen and lymph node cells of mice infected with L. braziliensis and LPG were capable to produce the cytokine IL-10 which has an important role in the regulation of the immune response. Besides, purified LPGs were not capable to activate intraperitoneal macrophages. However, when added together with LPS and IFN-?, LPGs were capable to alter the production of NO or IL-10. LPG from L. braziliensis has a dose-dependent effect in activated macrophages reducing the production of NO. On the other hand, LPG from L. amazonensis decrased the production of IL-10 by activated macrophages. In spite of these effects, the studied LPGs were not capable to modify the expression of molecules involved in the activation, presentation and cellular migration of macrophages. TLR2 does not seem to be required for observed effects. Our work contributes for the elucidation of the complex mechanisms that involve the immune response of the host and consequently the cure or resistance in Leishmania infections