Navegando por Palavras-chave "Leishmania (Leishmania) amazonensis"

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    Analysis and chromosomal mapping of Leishmania (Leishmania) amazonensis amastigote expressed sequence tags
    (Instituto Oswaldo Cruz, Ministério da Saúde, 2007-09-01) Gentil, Luciana Girotto [UNIFESP]; Lasakosvitsch, Fernanda [UNIFESP]; Franco da Silveira, José [UNIFESP]; Santos, Márcia Regina Machado dos [UNIFESP]; Barbiéri, Clara Lúcia [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    The characterization of expressed sequence tags (ESTs) generated from a cDNA library of Leishmania (Leishmania) amazonensis amastigotes is described. The sequencing of 93 clones generated new L. (L.) amazonensis ESTs from which 32% are not related to any other sequences in database and 68% presented significant similarities to known genes. The chromosome localization of some L. (L.) amazonensis ESTs was also determined in L. (L.) amazonensis and L. (L.) major. The characterization of these ESTs is suitable for the genome physical mapping, as well as for the identification of genes encoding cysteine proteinases implicated with protective immune responses in leishmaniasis.
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    Anticorpos monoclonais dirigidos a antígenos lipídicos estágio-específicos de formas promastigotas de Leishmania (Leishmania) amazonensis
    (Universidade Federal de São Paulo (UNIFESP), 2006-12-31) Peder, Leyde Daiane de [UNIFESP]; Straus, Anita Hilda [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    In order to obtain information about the lipid expression of promastigote forms of Leishmania (Leishmania) amazonensis, the parasites lipid composition profile was analyzed during log and stationary phase. Two monoclonal antibodies (mAb) termed LST-1 and LST-2 were produced, characterized and used in this study. Promastigote phospholipid expression on log and stationary growth phases were analyzed by high performance thin layer chromatography (HPTLC). At either phase the total lipid extract of L. (L.) amazonensis promastigotes presents phosphatidylinostol (PI), phosphatidylserine (PS), phosphatidylcholine (PC) phosphatidylethanolamine (PE), Lyso- PI and inositol phosphorylceramide (IPC). IPC was characterized by GC/MS, and it was detected sphingosine (d18:1) and fatty acids, mainly palmitic acid (C16:0), and stearic acid (C18:0). It was noted that the molar proportions of IPC, PS, PE and Lyso-PI increased during the culture time, while the percentage of PI and PC decreased. Unlikely, the glycolipid chromatographic profile did not change during the promastigotes growth at log and stationary phases. The mAbs LST-1 and LST-2 were produced against a glycolipid and IPC enriched fraction purified from promastigote forms of L. (L.) amazonensis. Both antibodies are IgM. By HPTLC immunostaining it was demonstrated that mAb LST-1 recognized an acidic lipid component, eluted with 0.2 M of sodium acetate from DEAE-Sephadex column. The LST-1 reactive component presents: i) chromatographic migration characteristic of IPC, ii) is resistant to alkaline hydrolysis; iii) is stained with Dittmer-Lester reagent. On the other hand, the mAb LST-2 was reactive with the glycolipid fraction not retained in DEAE-Sephadex column, and this fraction was visualized on HPTLC by primuline and orcinol/H2SO4 staining. By indirect immunofluorescence, both antibodies showed high reactivity with L. (L.) amazonensis promastigotes. Parasites delipidation with isopropanol:hexane:water (55:20:25; v/v/v), abolished the mAbs reactivity, indicating that the antigens recognized by LST-1 and LST-2 are present exclusively in the lipid fraction. MAb LST-1 did not react with non-fixed parasites, suggesting that IPC is cryptic in the membrane, and maybe localized only in the inner leaf of plasma membrane. Contrasting, mAb LST-2, showed a strong reactivity with live L. (L.) amazonensis promastigotes, also parasite agglutination was observed, indicating that the glycolipids recognized by LST-2 are in parasite surface. By indirect immunofluorescence with LST-1 and LST-2 no reactivity was observed with amastigotes isolated from L. (L.) amazonensis infected hamsters, conversely axenic amastigotes showed a strong fluorescence with both mAbs. By HPTLC it was verified that the lipid fractions of promastigotes, axenic amastigotes and amastigotes isolated from footpad lesions, presented distinct glycolipids and phospholipids profiles. Amastigotes isolated from lesions are rich in glycosphingolipids, whereas axenic amastigotes and promastigotes present glycoinositolphospholipids (GIPLs) recognized by LST-2, and IPC recognized by mAb LST-1. The LST-1 antibody recognized promastigotes from all species of analyzed, and also T. cruzi epimastigotes. It was determined that LST-1 recognizes specifically IPC in these parasites, and it was established that the inositol residue and the ceramide are essential for LST-1 reactivity. By indirect immunofluorescence with mAb LST-2 a strong labeling of only L. (L.) amazonensis promastigotes and axenic amastigotes was observed. LST-2 recognizes 4 glycolipid components termed a, b, c and d, which correspond to GIPLs. It was demonstrated that the carbohydrate moiety is fundamental for LST-2 reactivity. L. (L.) amazonensis promastigotes infected macrophages showed by indirect immunofluorescence, that promastigotes during the macrophage adhesion/infection, secrete or transfer GIPLs recognized by mAb LST-2 to the macrophage. Strong fluorescence in infected macrophage was observed in the first hours of infection. During the next hours of infection (up to 4 hours) also small fluorescent vesicles were observed in the infected macrophages, which did not correspond to phagossomes containing parasites. Thus, these studies describe distinct (glyco)phospholipid profile in lesion amastigotes, axenic amastigotes and promastigotes, and GIPLs vesicles formation during macrophage infection by promastigotes.
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    Avaliação das mudanças morfológicas e perfis fosfolipídicos de formas de Leishmania (Leishmania) amazonensis induzidas por variações de pH e temperatura nas condições de cultivo
    (Universidade Federal de São Paulo, 2021) Maciel, Leticia de Oliveira; Straus, Anita Hilda [UNIFESP]; http://lattes.cnpq.br/5581342220032436; http://lattes.cnpq.br/6413739829887678
    Leishmania apresenta dois estágios no ciclo de vida desenvolvidos em microambiente distintos. Nos insetos os parasitas encontram-se no trato digestivo e no hospedeiro vertebrado no vacúolo parasitóforo de células do sistema monocítico fagocitário. No presente estudo avaliou-se os efeitos de temperatura e pH, em culturas de Leishmania (Leishmania) amazonensis, quanto a morfologia dos parasitas, secreção de vesículas e expressão de fosfolipídeos. Os estudos foram realizados com formas promastigotas isoladas no início da fase estacionária e cultivadas por 48h em duas condições: i) controle, a 23 ̊C em meio pH 7,2 (mimetizando as condições do vetor invertebrado), e ii) em meio pH 5,5 a 35°C (mimetizando as condições dos fagolisossomos). Por microscopia confocal e microscopia eletrônica de varredura, diferenças morfológicas foram observadas já nas primeiras 12h após a transferência dos parasitas para meio acídico a 35˚C, com redução do tamanho do corpo e flagelo, e aparecimento de vesículas na superfície dos parasitas. Após 48h em meio pH 5,5 a 35˚C os parasitas se apresentaram com forma ovoide, com redução significante do comprimento do corpo e flagelo, cerca de 3,2 e 14 vezes, respectivamente. Esses parasitas foram caracterizados morfologicamente como “amastigota-like”. Após 48h observou-se aumento expressivo do número de vesículas na superfície dos “amastigotas-like”, essas vesículas não estavam presentes em parasitas mantidos pelo mesmo período de tempo em meio pH 7,2 a 23˚C. A presença de vesículas extracelulares foi avaliada em sobrenadante de 48h. Estas vesículas foram purificadas por centrifugações sequenciais e analisadas por microscopia de varredura. Somente os sobrenadantes das culturas em meio pH 5,5 a 35˚C apresentaram vesículas, com diâmetro médio de 63 nm, tamanho característico de exossomos. A expressão de inositolfosforilceramida (IPC) durante a diferenciação de promastigotas a “amastigotas-like” foi avaliada por microscopia confocal com o anticorpo monoclonal LST-1, anti-IPC. Forte marcação com LST-1 foi observada na membrana plasmática e em organelas intracelulares ainda não caracterizadas. Concomitantemente com a redução do tamanho do parasita, observou-se uma menor redução da marcação dos parasitas com LST-1. A expressão dos fosfolipídeos foi analisada, tanto em promastigotas quanto em “amastigotas-like”, foi analisada. Lipídeos foram extraídos dos parasitas, purificados e quantificados por cromatografia em camada delgada de alta resolução. Os “amastigotas-like” apresentam cerca de duas vezes menos fosfolipídeos que os promastigotas, considerando-se massa de fosfolipídeos/parasita, o que pode ser explicado pela redução do tamanho dos parasitas e secreção de vesículas pelos parasitas. Em relação a expressão de fosfolipídeos não detectamos diferenças significativas entre os perfis. Considerando-se as classes de fosfatidiletanolamina, fosfatidilcolina, fosfatidilinositol e inositolfosforilceramida entre as formas promastigotas e “amastigotas-like”, apesar de ter sido observada uma tendência de redução da expressão de IPC nos “amastigotas-like”, esfingolipídeo pouco expresso em amastigotas de lesão. Estudos ainda devem ser conduzidos visando análise mais detalhada sobre as diferentes espécies de cada classe, por espectrometria massas. Nossos resultados mostram claramente que a diferenciação do promastigotas em meio acídico em temperatura de 35˚C é acompanhada de extensa secreção de vesículas, com a redução do tamanho do parasita e do flagelo.
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    Avaliação do potencial leishmanicida do extrato das folhas de Eugenia pyriformis Cambess. (Myrtaceae) e de metabólitos secundários de fungos de diferentes biomas brasileiros
    (Universidade Federal de São Paulo, 2024-07-05) Zauli, Rogéria Cristina [UNIFESP]; Batista, Patricia Xander [UNIFESP]; Pascoal, Aislan Cristina Rheder Fagundes; Vasconcellos, Suzan Pantaroto de; http://lattes.cnpq.br/3620553457348403
    No Brasil, Leishmania (Leishmania) amazonensis é uma das espécies responsáveis pela forma mais comum da doença, a leishmaniose cutânea. Atualmente, existem poucas opções terapêuticas disponíveis para o tratamento da leishmaniose cutânea. O tratamento preconizado pelo Ministério da Saúde é realizado com fármacos tóxicos, de alto custo e de longa duração. Nesse sentido, a busca por novas alternativas terapêuticas para o tratamento da leishmaniose é de grande relevância. A biodiversidade da flora e de microrganismos no Brasil é bastante grande e há a necessidade de maior exploração desse potencial para o tratamento de doenças infecciosas e parasitárias. Assim, o objetivo desse trabalho foi avaliar o potencial anti-Leishmania de 6 extratos de folhas da Eugenia pyriformis Cambess. e de 108 extratos de fungos endofíticos coletados nos diferentes biomas brasileiros. Extrato bruto das folhas de E. pyriformis Cambess. coletadas no verão e quatro extratos de fungos endofíticos de diferentes biomas brasileiros (CG2-4, CG2-12, LHR-446 e BRA-05) apresentaram o maior índice de seletividade para a cepa de parasita testada. Com o uso da ferramenta citometria de fluxo, os parasitas tratados com os extratos selecionados demonstraram parada na fase inicial da replicação do ciclo celular e morte por necrose e/ou apoptose. Os fungos isolados dos biomas Caatinga e Cerrado são da espécie Aspergillus fumigatus, identificados por espectrometria de massas (Maldi Tof) e os extratos do bioma Amazônia foram provenientes do fungo Diaporthe cerradensis. E. pyriformis Cambess. não apresentou efeito no potencial de membrana mitocondrial de promastigotas, não utilizando essa via no mecanismo de ação. Já os extratos fúngicos reduziram o potencial de membrana mitocondrial em até 86%. A produção de NO foi aumentada após tratamento in vitro com os extratos fúngicos CG2-4, LHR-446 e BRA-05. Na leishmaniose cutânea experimental em camundongos BALB/c, BRA-05 foi bastante efetivo, sem causar progressão da doença e com redução significativa da carga parasitária. Neste estudo, alguns compostos majoritários foram identificados nos extratos da E. pyriformis Cambess., os quais são pertencentes ao grupo dos terpenóides e flavonóides, compostos comuns encontrados nessa família de plantas. Porém, o composto loliolide, pouco descrito nessa família, foi anotado nas frações mais eficazes contra essa cepa de Leishmania (L.) amazonensis. Os compostos majoritários anotados dos extratos do Cerrado (BRA-05) e Caatinga (LHR-446) são do grupo dos alcalóides e meroterpenóides. Três compostos anotados no extrato BRA-05 são inéditos para A. fumigatus. Em conclusão, neste trabalho foi realizado um amplo screening utilizando extratos de uma planta da biodiversidade brasileira e extratos de fungos endofíticos isolados de diferentes biomas do Brasil. O extrato com melhor atividade leishmanicida in vitro foi o BRA-05 e os testes com infecção experimental também evidenciaram essa atividade anti-Leishmania.
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    Efeito do tratamento com o complexo paladaciclo DPPE 1.1 associado ao DPPE 1.2 sobre a infecção pela Leishmania (Leishmania) amazonensis in vitro e in vivo
    (Universidade Federal de São Paulo (UNIFESP), 2016-10-31) Motta, Priscila Dias [UNIFESP]; Mestriner, Clara Lúcia Barbiéri [UNIFESP]; http://lattes.cnpq.br/7853993193464519; http://lattes.cnpq.br/6207910002977770; Universidade Federal de São Paulo (UNIFESP)
    The present study evaluated the efficacy of the treatment with the pallladacycle complex DPPE 1.1 associated to DPPE 1.2 on in vitro and in vivo Leishmania (Leishmania) amazonensis infection. The determination of the pharmacodynamic interaction of the two associated compounds in vitro was performed by use of DPPE 1.1 and DPPE 1.2 given alone or combined for the treatment of BALB/c bone marrow macrophages infected with L. (L.) amazonensis. In a first screening only one value of the fractional inhibitory concentration (FIC) of DPPE 1.1 and DPPE 1.2 was used and the data showed a synergistic effect between them. However, the fixed-ratio isobologram method leads to a higher reproducibility for drug interaction studies. So, the association between DPPE 1.1 and DPPE 1.2 was evaluated using this method and several FIC values were determined. The FICs were used for construction of a fixed-ratio isobologram which indicated an indifferent or additive interaction for DPPE 1.1 combined with DPPE 1.2. The in vivo treatment with DPPE 1.1, DPPE 1.2 or both associated was performed in L. (L.) amazonensis-infected BALB/c mice. In a first assay, the reduction of parasite load in animals treated with DPPE 1.1 associated with DPPE 1.2 was 50 fold higher than that estimated in mice treated with the same doses of DPPE 1.1 and DPPE 1.2 alone. Next, the ED50 was initially determined for each of the drugs given alone. Based on their ED50 values, different proportions of DPPE 1.1 associated with DPPE 1.2 were tested for determination of the ED50 of the drugs in combination whose values were used to calculate the activity enhancement index (AEI). The AEI indicated that DPPE 1.1 and DPPE 1.2 have possibly synergistic effect in vivo. The leishmanicidal activity in mice treated with DPPE 1.1 and DPPE 1.2 alone or associated was followed by a significant increase of T CD4+ lymphocytes. Treated mice also exhibited a small but not significant increase of T CD8+ lymphocytes. All treated mice displayed significantly lower levels of active TGF-? and higher of IFN-? compared to untreated controls, indicating a predominance of inflammatory responses in treated animals.
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    Imunolocalização de (glico)lipídeos de amastigotas de Leishmania (Leishmania) amazonensis e em macrófagos infectados
    (Universidade Federal de São Paulo, 2023-10-30) Nascimento, Paloma Angelin [UNIFESP]; Straus, Anita Hilda [UNIFESP]; http://lattes.cnpq.br/5581342220032436; http://lattes.cnpq.br/7420435798099223
    Visando melhor compreender o papel de glicoconjugados na patogenia da leishmaniose cutânea, foi avaliada por microscopia confocal a reatividade de anticorpos monoclonais (mAbs) em infecções de culturas de macrófagos derivados de medula óssea de camundongos BALB/c, com L. (L.) amazonensis. Foram avaliadas infecções com formas amastigotas isoladas de lesão de hamster e “amastigotas-like”, obtidas de culturas de promastigotas em meio acídico mantidas por 48h a 35˚C. As formas “amastigotas-like” mostraram ser altamente infectivas “in vitro” quando comparadas com as formas promastigotas. Por microscopia eletrônica de varredura verificou-se que a superfície dos amastigotas isolados de lesão apresentam alta densidade de corpos multivesiculares, como descrito para as formas “amastigota-like”, distinguindo-se da superfície de promastigotas, o que poderia contribuir para a maior infectividade dessas formas. Infecções de 4h foram avaliadas por imunofluorescência indireta, utilizando-se mAbs direcionados contra a porção glicana de compostos lipídicos, tais como: o lipofosfoglicano, reconhecido pelo mAb VST-1; glicosilinositolfosfolipídeos reconhecidos pelo mAb LST-2, ambos antígenos expressos preferencialmente em formas promastigotas; glicoesfingolipídeos expressos exclusivamente em formas amastigotas de L. (L.) amazonensis e reconhecidos pelos mAbs ST-3 e ST-5. Foi demonstrado que após a infecção forte marcação com o mAb VST-1 é detectada em macrófagos infectados com formas “amastigotas-like” e promastigotas, sugerindo que moléculas contendo o epítopo reconhecido por este mAb são liberadas/secretadas pelo parasita. Por outro lado, para os mAbs ST-3 e ST-5, a marcação é restrita à superfície dos amastigotas isolados de lesão. Os resultados dessa dissertação sugerem que essas três classes de glicoconjugados avaliadas, estão envolvidas em mecanismos distintos da modulação de macrófagos durante a infecção. Os resultados abrem novas perspectivas para a melhor compreensão do papel desses glicoconjugados na infecção pela L. (L.) amazonensis, poderá contribuir para o desenvolvimento de novas estratégias de controle da leishmaniose causada por esse parasita.
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    Partial protective responses induced by a recombinant cysteine proteinase from Leishmania (Leishmania) amazonensis in a murine model of cutaneous leishmaniasis
    (Elsevier B.V., 2010-02-01) Cardoso Fedeli, Carlos Eduardo; Ferreira, Josie Haydée Lima [UNIFESP]; Mussalem, Juliana Sekeres; Longo-Maugeri, Ieda Maria; Gentil, Luciana Girotto; Machado dos Santos, Marcia Regina; Katz, Simone; Barbieri, Clara Lucia [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Univ Fed Piaui; Univ Bandeirante São Paulo
    A 500 bp fragment encoding an isoform of cysteine proteinase from Leishmania (Leishmania) amazonensis was subcloned and expressed in the pHis vector, resulting in a recombinant protein of 24 kDa, rLacys24. in Western blots of L (L) amazonensis extracts, antibodies directed to rLacys24 recognized a cysteine proteinase isoform of 30 kDa. Analysis by fluorescence-activated cell sorter showed a significantly higher expression of CD8(+) lymphocytes in animals immunized with rLacys24 plus CFA, whereas a low expression of CD4(+) lymphocytes was observed in these animals. the cytotoxicity of lymphocytes isolated from mice immunized with rLacys24 plus CFA on L. (L.) amazonensis-infected macrophages was significantly higher than that observed in the presence of lymphocytes from control animals. Immunization of BALB/c mice with rLacys24 plus CFA resulted in a low but significant decrease of foot lesions after challenge with L (L) amazonensis compared to those exhibited by control mice. (C) 2009 Elsevier Inc. All rights reserved.
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    Preparação e caracterização de derivados da 8-hidroxiquinolina e avaliação de suas atividades leishmanicidas utilizando a espécie Leishmania (Leishmania) amazonensis
    (Universidade Federal de São Paulo, 2016-10-19) Silva, Etyene Janyne Gonzalez da [UNIFESP]; Raminelli, Cristiano [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Quinoline core is present in several biologically active substances. According to the literature 8-hydroxyquinoline has presented significant leishmanicidal activity against promastigote and amastigote forms of three species of Leishmania, including Leishmania (L.) amazonensis. Drugs used in the treatment of leishmaniasis have presented limitations such as, low efficiency and high toxicity, making necessary the searching for novel bioactive compounds. In this context, twenty-two compounds were evaluated against promastigote form of Leishmania (Leishmania) amazonensis, including three commercially available 8-hydroxyquinoline compounds and nineteen derivatives obtained through iodination, alkylation, and acylation reactions. The results of effective concentration 50% (EC50) obtained for the substances were compared with the EC50 value obtained for the amphotericin B, used as standard and, currently, employed in the treatment of leishmaniasis. The EC50 value obtained for 8-hydroxyquinoline was compared with the value described in the literature. Additionally, all compounds evaluated in this study showed leishmanicidal action with EC50 values ? 9.53 µg/mL, being considered biologically actives against promastigote form of L. (L.) amazonensis.
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    Role of Leishmania (Leishmania) amazonensis amastigote glycosphingolipids in macrophage infectivity
    (Associação Brasileira de Divulgação Científica, 2007-06-01) Tanaka, Améria Kaori [UNIFESP]; Gorin, Philip Albert James; Takahashi, Helio Kiyoshi [UNIFESP]; Straus, Anita Hilda [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Universidade Federal do Paraná Departamento de Bioquímica
    The role of glycosphingolipids (GSLs) present in amastigote forms of Leishmania (Leishmania) amazonensis during infection of macrophages was analyzed, with particular emphasis on GSLs presenting the terminal Galpß1-3Galpa disaccharide. Macrophage invasion by L. (L.) amazonensis amastigotes was reduced by 37% when the disaccharide Galpß1-3Galp (1 mM) was added to the culture medium. The putative macrophage receptor/lectin for ß-Gal-globotriaosylceramide (Galpß1-3Galpa1-4Galpß1-4Glc pß1-1Cer) and other structurally related GSLs from L. (L.) amazonensis amastigotes were analyzed by micelles and parasite binding assay to peritoneal macrophage proteins fractionated by SDS-PAGE under nonreducing conditions. Micelles containing purified amastigote GSLs or a suspention of L. (L.) amazonensis amastigotes fixed with 2% formaldehyde were incubated with nitrocellulose membrane containing the macrophage proteins transferred by Western blotting. Binding of micelles containing purified GSLs from amastigote forms or fixed L. (L.) amazonensis amastigotes to nitrocellulose membrane was probed using monoclonal antibody ST-3, which recognizes the glycoepitope Galpß1-3Galpa1-R present either in the micelle preparation or on the amastigote surface. Macrophage protein with molecular mass ~30 kDa bound the amastigote GSL and appeared to be a doublet on electrophoresis. The specificity of this interaction was confirmed using fixed L. (L.) chagasi amastigotes, which do not express GSLs such as ß-Galp-globotriaosylceramides, and which do not bind to 30-kDa protein.
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    Treatment of Leishmania (Leishmania) Amazonensis-Infected Mice with a Combination of a Palladacycle Complex and Heat-Killed Propionibacterium acnes Triggers Protective Cellular Immune Responses
    (Frontiers Media Sa, 2017) Paladi, Carolina S. [UNIFESP]; da Silva, Danielle A. M. [UNIFESP]; Motta, Priscila D. [UNIFESP]; Garcia, Daniel M. [UNIFESP]; Teixeira, Daniela [UNIFESP]; Longo-Maugeri, Ieda M. [UNIFESP]; Katz, Simone [UNIFESP]; Barbieri, Clara L. [UNIFESP]
    Palladacycle complex DPPE 1.2 was previously reported to inhibit the in vitro and in vivo infection by Leishmania (Leishmania) amazonensis. The aim of the present study was to compare the effect of DPPE 1.2, in association with heat-killed Propionibacterium acnes, on L. (L.) amazonensis infection in two mouse strains, BALB/c and C57BL/6, and to evaluate the immune responses of the treated animals. Foot lesions of L. (L.) amazonensis-infected mice were injected with DPPE 1.2 alone, or associated with P. acnes as an adjuvant. Analysis of T-cell populations in the treated mice and in untreated controls was performed by FACS. Detection of IFN-gamma-secreting lymphocytes was carried out by an ELISPOT assay and active TGF-beta was measured by means of a double-sandwich ELISA test. The treatment with DPPE 1.2 resulted in a significant reduction of foot lesion sizes and parasite burdens in both mouse strains, and the lowest parasite burden was found in mice treated with DPPE 1.2 plus P. acnes. Mice treated with DPPE 1.2 alone displayed a significant increase of TCD4(+) and TCD8(+) lymphocytes and IFN-gamma secretion which were significantly higher in animals treated with DPPE 1.2 plus P. acnes. A significant reduction of active TGF-b was observed in mice treated with DPPE 1.2 alone or associated with P. acnes. Moreover, DPPE 1.2 associated to P. acnes was non-toxic to treated animals. The destruction of L. (L.) amazonensis by DPPE 1.2 was followed by host inflammatory responses which were exacerbated when the palladacycle complex was associated with P. acnes.