Les cellules dendritiques plasmacytoides (pDCs), spécialisées dans la réponse antivirale, produisent de fortes quantités d’interféron (IFN) lorsqu’elles sont en contact avec des cellules infectées par des virus. Pourtant, les pDCs sont réfractaires à l’infection. Ce mécanisme d’activation de la réponse antivirale par le contact physique avec les cellules infectées, nouvellement découvert, constituerait un aspect général des voies de défense de l’hôte contre les virus.En utilisant le virus de l’Hépatite C et de la Dengue comme modèle viral, nous avons observé une réorganisation moléculaire au niveau des contacts entre les pDCs et les cellules infectées. La polarisation d’éléments cellulaires, notamment de régulateurs du cytosquelette d’actine et de molécules de la machinerie d’endocytose en direction du contact favoriserait son établissement et/ou sa stabilisation ainsi qu’une transmission efficace d’éléments viraux, ensuite reconnus par les pDCs. Nous avons également démontré que les pDCs effectuent des contacts plus stables et présentent une polarisation plus importante d’éléments cellulaires aux contacts avec des cellules infectées qu’avec des cellules non infectées. Ces interactions présentent des similarités avec les synapses, contacts cellulaires organisés impliqués dans la communication cellulaire. Notamment, les synapses immunologiques jouent un rôle important dans l’activation de la réponse immunitaire adaptative. Nous proposons donc de nommer ces contacts activateurs de pDCs des « synapses immunologiques innées ». Ce mécanisme représenterait un processus de reconnaissance des infections par les pDCs généralisable à différents types de virus, par « scan » du statut infectieux des cellules par contact. Nos résultats suggèrent également que des éléments viraux s’accumulent au niveau de ces contacts. Ces éléments diffèrent en fonction du type d’infection. Notamment, nous avons mis en évidence dans un contexte d’infection par le virus de la Dengue que des structures virales non canoniques et non infectieuses, différentes des particules virales infectieuses dites « classiques », jouent un rôle important dans l’activation de la réponse antivirale. Notre travail apporte un nouvel angle d’analyse de l’activation des pDCs et des stratégies de détection des infections virales par l’hôte. / Plasmacytoid dendritic cells (pDCs), specialized in the antiviral response, are important producers of interferons (IFN) after cell-cell contacts with virally infected cells. Nonetheless, they are poorly permissive to the majority of viral infections. This newly uncovered mechanism of the activation of an antiviral response by physical cell-cell contacts with infected cells could constitute a general aspect of the host defense against viral infections.Using Hepatitis C virus and Dengue virus as models, we observed a molecular reorganization of the contacts between pDCs and infected cells. The polarization toward contacts of cellular elements, such as regulators of the actin cytoskeleton and components of the endocytic machinery could favor their establishment and/or their stabilization, as well as the efficient transmission of viral elements that are recognized by pDCs. We also demonstrated that pDCs contacts with infected cells are more stable and present a higher polarization of cellular components than contacts with uninfected cells. These interactions present similarities with synapses, a type of organized contact involved in cell-to-cell communication. Notably, immunological synapses are known to play an important role in the activation of the adaptive immune response. We thus propose to call these pDC-activating contacts « innate immunological synapses ». This mechanism could represent a general process of recognition of viral infections by pDCs, by « scanning » the infectious status of the cells by cell-cell contacts. Our results also suggest that viral elements cluster at the level of contacts. These elements differ depending on the type of viral infection. Notably, we observed in the context of Dengue virus infection that non-infectious non-canonical viral structures, that differ from the « classical » viral infectious particles, play an important role in the activation of the antiviral response. Our work brings a new light in the mechanisms of pDC activation and in the host defense strategies against viral infection.

Orientador: Alessandro Francisco Talamini do Amarante / Banca: Lucia Helena O'Dwyer de Oliveira / Banca: Elizabeth Moreira dos Santos Shmidt / Banca: Vamilton Alvares Santarém / Banca: Ricardo Velludo Gomes de Soutello / Resumo: Este trabalho foi desenvolvido com o objetivo de avaliar a resistência natural aos endoparasitas e ectoparasitas em bovinos da raça Crioula Lageana e meio-sangue Angus. Foram utilizados 10 machos castrados em cada grupo, desmamados (6-8 meses), mantidos juntos em pastagens cultivadas no município de Monte Castelo - SC. A cada 28 dias, fêmeas de carrapatos com tamanho acima de 4 mm foram quantificadas nos lados direito e esquerdo do corpo de cada animal. O mesmo foi feito para nódulos de Dermatobia hominis. A espessura da capa do pelame foi também avaliada a cada coleta e os animais foram classificados quanto à coloração do pelame. Foram coletadas amostras de fezes para realização de exames coproparasitológicos e de sangue para quantificação de anticorpos, bem como realizada a pesagem dos animais nessas mesmas ocasiões. Os animais foram abatidos e deles coletadas alíquotas dos conteúdos gastrintestinais para contagem e identificação dos parasitas. Os animais da raça Crioula Lageana apresentaram menores infestações por larvas de D. hominis e Rhipicephalus (Boophilus) microplus. Não houve diferença entre a disposição de carrapatos e bernes conforme os lados do corpo. Os animais de pelagem escura foram mais susceptíveis aos ectoparasitas. Não houve diferença significativa na carga parasitária entre animais da raça Crioula Lageana e meio-sangue Angus. A partir dos 18 meses de idade os animais de ambas as raças mantiveram baixos valores de OPG, dados que sugerem a aquisição de imunidade contra as infecções por nematódeos devido aos constantes desafios / Abstract: This study was carried out to evaluate the natural breed resistance against nematode infections and ectoparasites infestations in Crioulo Lageano and crossbred Angus male calves. Ten weaned calves (6-8 months) were used in each group and were kept together in winter and summer pastures in Monte Castelo, Santa Catarina State. Every 28 days, female ticks more then 4 mm long were counted on the right and left side of the body of each animal, as well as the Dermatobia hominis nodules. Coat thickness also was measured at each sampling and all animals were classified according coat color. Fecal and blood samples were collected for parasitological and immunological tests. Body weight was recorded in the same occasion. All animals were slaughtered and gastrointestinal contents were collected from each individual for quantification and identification of parasites. Crioulo Lageano group was less infested by D. hominis and by Rhipicephalus (Boophilus) microplus. There were no differences in the distribution of the ticks and grubs between animal body sides. Dark-haired animal in both groups were the most susceptible. There were no significant differences in worm burden between the Crioula and crossbred Angus groups. From 18 months of age, Crioula Lageana and crossbred Angus animals kept low fecal egg counts. These data suggest that the animals acquired immunity resistance against nematode infections, due to constant challenges / Doutor

Made available in DSpace on 2017-05-12T14:36:24Z (GMT). No. of bitstreams: 1 Dissertacao Iara _Fernanda Rocha (1).pdf: 1203704 bytes, checksum: 3b3c626c8325feae1cf11ce8968fd774 (MD5) Previous issue date: 2015-12-03 / Diatraea saccharalis is an important insect pest of sugarcane and other crops, so it has been the focus of research. In general, the insects present innate immune system, which come with a range of immune responses against microorganisms. Many antimicrobial peptides have been isolated and characterized from model insects such as Drosophila melanogaster and Bombyx mori. In the 5th instar larvae of Diatraea saccharalis has already been reported a protein of Gloverin family with antimicrobial activity. Considering these facts, the objectives of this study were to determine the protein profile of hemolymph larvae from Diatraea sacharalis at 5th instar challenged with Escherichia coli (ATCC 11224) and Bacillus subtilis (ATCC 6623), identify differentially expressed proteins and polypeptides by analyzing the proteomic data, and verifying the antimicrobial activity of crude extract on plates by inhibition of microbial growth. Proteins from the hemolymph of larvae of D. sacharalis challenged and unchallenged were extracted. The samples were quantified and subjected to two-dimensional electrophoresis (2-DE) to obtain a proteomic profile of native hemolymph, challenged by E. coli and B. subtilis. Each gel showed an average of 300 protein spots and 92 spots were correspondents in these gels on three conditions. Were taken 41 different protein spots from gels, these spots were digested with trypsin and analyzed by mass spectrometry of the type MALDI-TOF/TOF. In this analysis, it was possible to identify 10 proteins from MS and MS/MS spectra. Among these proteins were expressed by induction with both bacteria such as chitinase and antimicrobial peptides: protein homologous to the turandot (turandot the like-protein), protein homologous to attacin (Attacin like-protein), and protein homologous peptidoglycan recognition. Another antimicrobial peptide was found, the homologous to β-defensin (β-defensin-like protein), induced only in the hemolymph of the larvae challenged by B. subtilis. A homologous protein Cyclophilin (Cyclophilin-like protein) was found in the hemolymph of larvae challenged and non-challenged. In addition, were also found proteins with hatching activity, hydrolytic not characterized and hypothetical protein of unknown function. Additionally, it also tested the antimicrobial activity of crude extracts from the hemolymph, by testing inhibition of microbial growth plate area, and this analysis was observed inhibition of growth of B. subtilis with the hemolymph extract from larvae challenged with B. subtilis. This is the first analysis of proteomic profile of hemolymph of a major agricultural pest, which verified the expression of some proteins with several functions and four related proteins immune response. These results contribute to the understanding of the immune system D. saccharalis under condition of infection. / Diatraea saccharalis é um importante inseto praga da cana-de-açúcar e de outras culturas agrícolas, por isso, tem sido foco de pesquisas. De uma forma geral, os insetos apresentam sistema imunológico inato, que os provêm com uma gama de respostas imunológicas contra microrganismos. Inúmeros peptídeos antimicrobianos têm sido isolados e caracterizados a partir de insetos modelo, como Bombyx mori e Drosophila melanogaster. Em larvas de 5º ínstar de Diatraea saccharalis já foi reportada uma proteína da família Gloverina com atividade antimicrobiana. Considerando estes fatos, os objetivos deste trabalho foram determinar o perfil de proteínas da hemolinfa de larvas de Diatraea sacharalis em 5º ínstar desafiadas com Escherichia coli (ATCC 11224) e Bacillus subtilis (ATCC 6623), identificar proteínas e polipeptídios diferencialmente expressos através da análise dos dados proteômicos, e verificar a atividade antimicrobiana do extrato bruto em placas por meio da inibição do crescimento microbiano. Foram extraídas proteínas da hemolinfa de larvas de D. sacharalis desafiadas e de não desafiadas. As amostras foram quantificadas e submetidas à eletroforese bidimensional (2-DE) para obtenção de um perfil proteômico da hemolinfa nativa, de larvas desafiadas por E. coli e B. subtilis. Cada gel apresentou em média 300 spots protéicos e 92 destes spots eram correspondentes nos géis nas três condições. Foram retirados 41 spots protéicos diferentes dos géis, estes spots foram digeridos com tripsina e analisados por espectrometria de massas do tipo Maldi-ToF/ToF. Nesta análise, foi possível identificar 10 proteínas a partir dos espectros MS e MS/MS. Entre elas, proteínas que foram expressas pela indução com ambas as bactérias, como a quitinase, e os peptídeos antimicrobianos: proteina homóloga à turandot A (turandot A like-protein), proteina homóloga à Atacina (Attacin like-protein), proteína homóloga de reconhecimento de peptideoglicano. Outro peptídeo antimicrobiano encontrado, o homólogo à β-defensina (β-defensin like-protein), foi induzido somente na hemolinfa das larvas desafiadas por B. subtilis. Uma proteína homológa á Ciclofilina (Cyclophilin like-protein) foi encontrada na hemolinfa da larvas desafiadas e não-desafiadas. Além disso, também foram encontradas proteínas com atividade de eclosão, hidrolítica, não caracterizada e proteína hipotética com função desconhecida. Adicionalmente, foi também testada a atividade antimicrobiana dos extratos brutos da hemolinfa, pelo ensaio de zona de inibição do crescimento microbiano em placa, e nesta análise, foi verificada a inibição do crescimento de B. subtilis com o extrato da hemolinfa de larvas desafiadas com B. subtilis. Esta é a primeira análise do perfil proteômico da hemolinfa de uma importante praga agrícola, na qual verificou-se a expressão de algumas proteínas com funções diversas e quatro proteínas relacionadas a resposta imunulógica. Estes resultados contribuem para a compreensão do sistema imunológico da D. saccharalis sob condição de infecção.

Made available in DSpace on 2017-07-10T13:59:27Z (GMT). No. of bitstreams: 1 Dissertacao Iara _Fernanda Rocha (1).pdf: 1203704 bytes, checksum: 3b3c626c8325feae1cf11ce8968fd774 (MD5) Previous issue date: 2015-12-03 / SIM (não especificado) / Diatraea saccharalis is an important insect pest of sugarcane and other crops, so it has been the focus of research. In general, the insects present innate immune system, which come with a range of immune responses against microorganisms. Many antimicrobial peptides have been isolated and characterized from model insects such as Drosophila melanogaster and Bombyx mori. In the 5th instar larvae of Diatraea saccharalis has already been reported a protein of Gloverin family with antimicrobial activity. Considering these facts, the objectives of this study were to determine the protein profile of hemolymph larvae from Diatraea sacharalis at 5th instar challenged with Escherichia coli (ATCC 11224) and Bacillus subtilis (ATCC 6623), identify differentially expressed proteins and polypeptides by analyzing the proteomic data, and verifying the antimicrobial activity of crude extract on plates by inhibition of microbial growth. Proteins from the hemolymph of larvae of D. sacharalis challenged and unchallenged were extracted. The samples were quantified and subjected to two-dimensional electrophoresis (2-DE) to obtain a proteomic profile of native hemolymph, challenged by E. coli and B. subtilis. Each gel showed an average of 300 protein spots and 92 spots were correspondents in these gels on three conditions. Were taken 41 different protein spots from gels, these spots were digested with trypsin and analyzed by mass spectrometry of the type MALDI-TOF/TOF. In this analysis, it was possible to identify 10 proteins from MS and MS/MS spectra. Among these proteins were expressed by induction with both bacteria such as chitinase and antimicrobial peptides: protein homologous to the turandot (turandot the like-protein), protein homologous to attacin (Attacin like-protein), and protein homologous peptidoglycan recognition. Another antimicrobial peptide was found, the homologous to β-defensin (β-defensin-like protein), induced only in the hemolymph of the larvae challenged by B. subtilis. A homologous protein Cyclophilin (Cyclophilin-like protein) was found in the hemolymph of larvae challenged and non-challenged. In addition, were also found proteins with hatching activity, hydrolytic not characterized and hypothetical protein of unknown function. Additionally, it also tested the antimicrobial activity of crude extracts from the hemolymph, by testing inhibition of microbial growth plate area, and this analysis was observed inhibition of growth of B. subtilis with the hemolymph extract from larvae challenged with B. subtilis. This is the first analysis of proteomic profile of hemolymph of a major agricultural pest, which verified the expression of some proteins with several functions and four related proteins immune response. These results contribute to the understanding of the immune system D. saccharalis under condition of infection. / Diatraea saccharalis é um importante inseto praga da cana-de-açúcar e de outras culturas agrícolas, por isso, tem sido foco de pesquisas. De uma forma geral, os insetos apresentam sistema imunológico inato, que os provêm com uma gama de respostas imunológicas contra microrganismos. Inúmeros peptídeos antimicrobianos têm sido isolados e caracterizados a partir de insetos modelo, como Bombyx mori e Drosophila melanogaster. Em larvas de 5º ínstar de Diatraea saccharalis já foi reportada uma proteína da família Gloverina com atividade antimicrobiana. Considerando estes fatos, os objetivos deste trabalho foram determinar o perfil de proteínas da hemolinfa de larvas de Diatraea sacharalis em 5º ínstar desafiadas com Escherichia coli (ATCC 11224) e Bacillus subtilis (ATCC 6623), identificar proteínas e polipeptídios diferencialmente expressos através da análise dos dados proteômicos, e verificar a atividade antimicrobiana do extrato bruto em placas por meio da inibição do crescimento microbiano. Foram extraídas proteínas da hemolinfa de larvas de D. sacharalis desafiadas e de não desafiadas. As amostras foram quantificadas e submetidas à eletroforese bidimensional (2-DE) para obtenção de um perfil proteômico da hemolinfa nativa, de larvas desafiadas por E. coli e B. subtilis. Cada gel apresentou em média 300 spots protéicos e 92 destes spots eram correspondentes nos géis nas três condições. Foram retirados 41 spots protéicos diferentes dos géis, estes spots foram digeridos com tripsina e analisados por espectrometria de massas do tipo Maldi-ToF/ToF. Nesta análise, foi possível identificar 10 proteínas a partir dos espectros MS e MS/MS. Entre elas, proteínas que foram expressas pela indução com ambas as bactérias, como a quitinase, e os peptídeos antimicrobianos: proteina homóloga à turandot A (turandot A like-protein), proteina homóloga à Atacina (Attacin like-protein), proteína homóloga de reconhecimento de peptideoglicano. Outro peptídeo antimicrobiano encontrado, o homólogo à β-defensina (β-defensin like-protein), foi induzido somente na hemolinfa das larvas desafiadas por B. subtilis. Uma proteína homológa á Ciclofilina (Cyclophilin like-protein) foi encontrada na hemolinfa da larvas desafiadas e não-desafiadas. Além disso, também foram encontradas proteínas com atividade de eclosão, hidrolítica, não caracterizada e proteína hipotética com função desconhecida. Adicionalmente, foi também testada a atividade antimicrobiana dos extratos brutos da hemolinfa, pelo ensaio de zona de inibição do crescimento microbiano em placa, e nesta análise, foi verificada a inibição do crescimento de B. subtilis com o extrato da hemolinfa de larvas desafiadas com B. subtilis. Esta é a primeira análise do perfil proteômico da hemolinfa de uma importante praga agrícola, na qual verificou-se a expressão de algumas proteínas com funções diversas e quatro proteínas relacionadas a resposta imunulógica. Estes resultados contribuem para a compreensão do sistema imunológico da D. saccharalis sob condição de infecção.

Carcinoma growth requires a supportive tumor stroma. The concept of reciprocal interactions between tumor and stromal cells has become widely acknowledged and the connective tissue activation seen in the malignant process has been likened to that of a healing wound. Little is, however, known about the specific characteristics of these interactions, distinguishing them from the interplay occurring between epithelial and stromal cells in wound healing. In order to study differences in the humoral effects of malignant and benign epithelial cells on fibroblasts, we used an in vitro coculture model with human oral squamous cell carcinoma cells (SCC) or normal oral keratinocytes (NOK) on one side of a semi-permeable membrane and fibroblasts seeded in gels on the other. Pro-collagens α1(I) and α1(III) were more downregulated in NOK cocultures compared to SCC cocultures. IL-1α was identified as a major keratinocyte-derived soluble factor behind the effects observed. We concluded that SCC are less antifibrotic compared to NOK. There was also a differential expression among enzymes involved in ECM turnover. The urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) were both upregulated by NOK, but not by SCC. Here, rIL-1ra caused further upregulation of PAI-1. Global gene expression in fibroblasts was assessed using Affymetrix™ arrays. In total, 82 transcripts were considered differentially expressed; 52 were up- and 30 were downregulated in SCC compared to NOK cocultures. Among the differentially expressed genes there was an enrichment of genes related to collagens and to a nonspecific, innate-type response. The innate response marker pentraxin (PTX3) was upregulated by keratinocyte-derrived IL-1α in both NOK and SCC cocultures. We observed a considerably higher IL-1α / IL-1ra quotient in SCC cocultures, however, while PTX3 mRNA upregulation was higher in SCC cocultures, there was no difference in the level of PTX3 secreted protein. Taken together, we concluded that NOK and SCC regulate genes important for ECM composition and for the innate immune-response differentially. IL-1α was identified as one important mediator of the observed effects. In general, SCC appeared to be more profibrotic in their effects on fibroblasts.

Made available in DSpace on 2014-06-11T19:31:28Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-10-25Bitstream added on 2014-06-13T19:20:32Z : No. of bitstreams: 1 cardoso_cp_dr_botfmvz.pdf: 1128230 bytes, checksum: beda813ceba29775170e003ab9fee808 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Este trabalho foi desenvolvido com o objetivo de avaliar a resistência natural aos endoparasitas e ectoparasitas em bovinos da raça Crioula Lageana e meio-sangue Angus. Foram utilizados 10 machos castrados em cada grupo, desmamados (6-8 meses), mantidos juntos em pastagens cultivadas no município de Monte Castelo – SC. A cada 28 dias, fêmeas de carrapatos com tamanho acima de 4 mm foram quantificadas nos lados direito e esquerdo do corpo de cada animal. O mesmo foi feito para nódulos de Dermatobia hominis. A espessura da capa do pelame foi também avaliada a cada coleta e os animais foram classificados quanto à coloração do pelame. Foram coletadas amostras de fezes para realização de exames coproparasitológicos e de sangue para quantificação de anticorpos, bem como realizada a pesagem dos animais nessas mesmas ocasiões. Os animais foram abatidos e deles coletadas alíquotas dos conteúdos gastrintestinais para contagem e identificação dos parasitas. Os animais da raça Crioula Lageana apresentaram menores infestações por larvas de D. hominis e Rhipicephalus (Boophilus) microplus. Não houve diferença entre a disposição de carrapatos e bernes conforme os lados do corpo. Os animais de pelagem escura foram mais susceptíveis aos ectoparasitas. Não houve diferença significativa na carga parasitária entre animais da raça Crioula Lageana e meio-sangue Angus. A partir dos 18 meses de idade os animais de ambas as raças mantiveram baixos valores de OPG, dados que sugerem a aquisição de imunidade contra as infecções por nematódeos devido aos constantes desafios / This study was carried out to evaluate the natural breed resistance against nematode infections and ectoparasites infestations in Crioulo Lageano and crossbred Angus male calves. Ten weaned calves (6-8 months) were used in each group and were kept together in winter and summer pastures in Monte Castelo, Santa Catarina State. Every 28 days, female ticks more then 4 mm long were counted on the right and left side of the body of each animal, as well as the Dermatobia hominis nodules. Coat thickness also was measured at each sampling and all animals were classified according coat color. Fecal and blood samples were collected for parasitological and immunological tests. Body weight was recorded in the same occasion. All animals were slaughtered and gastrointestinal contents were collected from each individual for quantification and identification of parasites. Crioulo Lageano group was less infested by D. hominis and by Rhipicephalus (Boophilus) microplus. There were no differences in the distribution of the ticks and grubs between animal body sides. Dark-haired animal in both groups were the most susceptible. There were no significant differences in worm burden between the Crioula and crossbred Angus groups. From 18 months of age, Crioula Lageana and crossbred Angus animals kept low fecal egg counts. These data suggest that the animals acquired immunity resistance against nematode infections, due to constant challenges

Submitted by isabela.moljf@hotmail.com (isabela.moljf@hotmail.com) on 2017-05-02T11:52:03Z No. of bitstreams: 1 julianeaparecidamarinhoduque.pdf: 731257 bytes, checksum: 33e3fa7ee51026581b189b467b6e0740 (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2017-05-12T15:52:16Z (GMT) No. of bitstreams: 1 julianeaparecidamarinhoduque.pdf: 731257 bytes, checksum: 33e3fa7ee51026581b189b467b6e0740 (MD5) / Made available in DSpace on 2017-05-12T15:52:16Z (GMT). No. of bitstreams: 1 julianeaparecidamarinhoduque.pdf: 731257 bytes, checksum: 33e3fa7ee51026581b189b467b6e0740 (MD5) Previous issue date: 2012-05-07 / CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / A malária é uma importante doença tropical com distribuição mundial. A doença é causada por protozoários do gênero Plasmodium que infectam humanos e outras espécies animais. Modelos experimentais de infecção por Plasmodium berghei NK65A (PbNK65A) em camundongos Balb/c auxiliam na compreensão da doença humana. A resposta imune à malária é extremamente complexa. Os macrófagos apresentam-se como importantes células no combate ao estágio eritrocítico do parasito. O trabalho buscou avaliar diferentes aspectos da função destas células durante a infecção por PbNK65. Os resultados demonstraram que a parasitose não altera a frequência relativa da população de macrófagos peritoneais nos camundongos. Porém, os animais infectados, apresentaram maior expressão de moléculas co-estimuladoras, principalmente CD80, e expressiva redução da capacidade de fagocitar hemácias parasitadas ao longo da infecção. A produção da IL-12, citocina importante para ativação da resposta celular também foi intensamente prejudicada pelo parasito no decorrer da infecção. Diante dos resultados, podemos sugerir que a infecção por Plasmodium berghei NK65 interfere na resposta imune inata, e esta pode ser atribuída ao caráter negativo da infecção sobre o macrófago, que possui suas principais funções alteradas, como a fagocitose e a produção de IL-12. Ainda que a co-estimulação seja preservada e até elevada neste modelo, é insuficiente para o hospedeiro gerar uma resposta celular eficiente que limitaria a proliferação de Plasmodium e, sobretudo, a morte do hospedeiro. / Malaria is a major tropical disease with worldwide distribution. The disease is caused by protozoa of the genus Plasmodium which infects humans and other animal species. Experimental models of infection by Plasmodium berghei NK65A (PbBNK65A) in Balb/c mice is important in the understanding of human disease. Immune response to malaria configures itself extremely, involving different elements. Macrophages are important cells against the erythrocytic parasite stage. Thus, the study aimed to evaluate different aspects of macrophage functions during infection by PbNK65A. The results showed that the parasite does not alter the frequency on peritoneal macrophages. However, the infected animals showed higher expression of coestimulatory molecules, mainly CD80 and significant reduction in the ability to phagocytosis infected erythrocytes during the infection. The production of IL-12 cytokine, important for activation of the cellular response, was also affected during infection. Thus, we suggest that infection by Plasmodium affects the innate immune response, and this can be attributed to the negative character of the infection on the macrophages, which has changed its principal functions, such as phagocytosis and IL-12 production. Although co-stimulation is preserved and even higher in this model, is insufficient to generate a host cell response that limits the proliferation of Plasmodium, and especially the host death.

Bowdichia virgilioides Kunth, popularly known as "sucupira preta", is used in folk regional medicine to combat inflammation, autoimmune diseases and healing. There are only few scientific studies dealing with its biological activity, especially in regards to the immune system, making it a potential target of scientific research. The aim of this study was to evaluate in vivo the action of the aqueous extract of Bowdichia virgilioides-derived stem bark (EaBv) in cellular and humoral responses. Swiss male mices were used (4-6 weeks), which were administered EaBv orally for 7 consecutive days. Initially using the template of zymosan A showed that treatment with EaBv increased phagocytic capacity of resident peritoneal macrophages. On the peripheral blood leukocytes count, it was observed a decrease in the number of total leukocytes in animals treated with EaBv and this reduction was observed when the differential number of neutrophils counts was performed. However, the increased number of lymphocytes in peripheral blood of animals after treatment. It has been found by the hemagglutination assay EaBv was able to decrease the production of antibodies. The extract stimulated proliferation of lymphocytes which have been obtained from lymph nodes after 7 days of treatment. Also, interfered with the effect of ConA on T lymphocyte proliferation and acted negatively on the action of LPS on the proliferation of B lymphocytes. Furthermore, flow cytometric, it was observed that the EaBv increased expression of TNF-α by T lymphocytes and IL-10 by B lymphocytes. However, expression of TNF-α by B lymphocytes has been modulated negatively by the extract. Together, these results suggest that aqueous extract of Bowdichia virgilioides-derived stem bark possesses a complexe immune activity, acting on the cellular and humoral immune responses. / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Bowdichia virgilioides Kunth, popularmente conhecida como sucupira-preta , é espécie utilizada na medicina popular regional no combate a inflamação, doenças auto-imunes e cicatrizante. Ainda são escassos os estudos que tratam da sua atividade biológica, principalmente em relação ao sistema imunológico, o que a torna um alvo em potencial de investigações científicas. O objetivo desse trabalho foi avaliar in vivo a ação do extrato aquoso da casca do caule da Bowdichia virgilioides (EaBv) na resposta imunológica celular e humoral. Foram utilizados camundongos Swiss (4-6 semanas) machos, aos quais foi administrado por via oral o EaBv durante 7 dias consecutivos. Inicialmente, utilizando o modelo de zimosan A demonstrou-se que o tratamento com EaBv aumentou a capacidade fagocítica de macrófagos peritoneais residentes. Na contagem de leucócitos do sangue periférico, observou-se uma diminuição no número de leucócitos totais nos animais tratados com EaBv e esta diminuição foi evidenciada no número de neutrófilos quando realizada a contagem diferencial. No entanto, o número de linfócitos aumentou no sangue periférico dos animais após o tratamento. Verificou-se pelo ensaio de hemaglutinação que o EaBv foi capaz de diminuir a produção de anticorpos. O extrato estimulou a proliferação dos linfócitos totais que foram obtidos dos linfonodos mesentéricos após os 7 dias de tratamento. Além disso, interferiu na ação da concanavalina A sobre a proliferação de linfócitos T, e agiu negativamente na ação do lipopolissacarídeo sobre a proliferação de linfócitos B. Ainda, por citometria de fluxo, observou-se que o EaBv aumentou a expressão das citocinas TNF-α nos linfócitos T e IL-10 nos linfócitos B. Entretanto, a expressão de TNF-α pelos linfócitos B foi modulado negativamente pelo extrato. Em conjunto, os resultados sugerem que o extrato aquoso da casca do caule Bowdichia virgilioides possui uma atividade imunológica complexa, agindo sobre as respostas imunes celular e humoral.