Browsing by Author "Oliveira, Milton Adriano Pelli de"

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    Coinfection with Toxoplasma gondii inhibits antigen-specific Th2 immune responses, tissue inflamation, and parasitism in BALB/c mice infected with Leishmania major.
    (1999) Santiago, Helton da Costa; Oliveira, Milton Adriano Pelli de; Bambirra, Eduardo Alves; Faria, Ana Maria Caetano de; Afonso, Luís Carlos Crocco; Oliveira, Leda Quercia; Gazzinelli, Ricardo Tostes
    Lesion size, cellular infiltration, and tissue parasitism in the footpads of BALB/c mice infected with Leishmania major were all dramatically inhibited during acute but not chronic infection with Toxoplasma gondii. Similarly, acute but not chronic toxoplasmosis at the time of infection with L. major had a strong inhibitory effect on development of acquired immune responses mediated by Th2 lymphocytes. In contrast, no m
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    Ecto-nucleotidase activities of promastigotes from leishmania (Viannia) braziliensis relates to parasite infectivity and disease clinical outcome.
    (2012) Leite, Pauline Martins; Gomes, Rodrigo Saar; Figueiredo, Amanda Braga de; Serafim, Tiago Donatelli; Tafuri, Wagner Luiz; Gomes, Carolina Cavaliéri; Moura, Sandra Aparecida Lima de; Fietto, Juliana Lopes Rangel; Melo, Maria Norma; Dias, Fátima Ribeiro; Oliveira, Milton Adriano Pelli de; Rabello, Ana Lúcia Teles; Afonso, Luís Carlos Crocco
    Background: Leishmania (Viannia) braziliensis has been associated with a broad range of clinical manifestations ranging from a simple cutaneous ulcer to destructive mucosal lesions. Factors leading to this diversity of clinical presentations are not clear, but parasite factors have lately been recognized as important in determining disease progression. Given the fact that the activity of ecto-nucleotidases correlates with parasitism and the development of infection, we evaluated the activity of these enzymes in promastigotes from 23 L. braziliensis isolates as a possible parasite-related factor that could influence the clinical outcome of the disease. Methodology/Principal Findings: Our results show that the isolates differ in their ability to hydrolyze adenine nucleotides. Furthermore, we observed a positive correlation between the time for peak of lesion development in C57BL/6J mice and enzymatic activity and clinical manifestation of the isolate. In addition, we found that L. (V.) braziliensis isolates obtained from mucosal lesions hydrolyze higher amounts of adenine nucleotides than isolates obtained from skin lesions. One isolate with high (PPS6m) and another with low (SSF) ecto-nucleotidase activity were chosen for further studies. Mice inoculated with PPS6m show delayed lesion development and present larger parasite loads than animals inoculated with the SSF isolate. In addition, PPS6m modulates the host immune response by inhibiting dendritic cell activation and NO production by activated J774 macrophages. Finally, we observed that the amastigote forms from PPS6m and SSF isolates present low enzymatic activity that does not interfere with NO production and parasite survival in macrophages. Conclusions/Significance: Our data suggest that ecto-nucleotidases present on the promastigote forms of the parasite may interfere with the establishment of the immune response with consequent impaired ability to control parasite dissemination and this may be an important factor in determining the clinical outcome of leishmaniasis.
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    Germ-free mice produce high levels of interferon-gamma in response to infection with Leishmania major but fail to heal lesions.
    (2005) Oliveira, Marcia Rosa de; Tafuri, Wagner Luiz; Afonso, Luís Carlos Crocco; Oliveira, Milton Adriano Pelli de; Nicoli, Jacques Robert; Vieira, Etel Rocha; Scott, Phillip; Melo, Maria Norma; Vieira, Leda Quercia
    In order to investigate the importance of the host microbiota on differentiation of T cell subsets in response to infection, Swiss/NIH germ-free mice and conventional (microbiota-bearing) mice were infected with Leishmania major, and lesion development, parasite loads, and cytokine production were assessed. Germ-free mice failed to heal lesions and presented a higher number of parasites at the site of infection than their conventional counterparts. In addition, histopathological analysis indicated a higher density of parasitized macrophages in lesions from germ-free mice than in conventional mice. The initial production of interleukin (IL)-12 and interferon-gamma (IFN-c) in germ-free mice was comparable to the conventional controls. Also, germ-free mice produced elevated levels of IFN-c and lower levels of IL-4 throughout the course of infection, suggesting the development of a Th1 response. Macrophages from germ-free mice exposed to IFN-c and infected with amastigotes in vitro were not as efficient at killing parasites as macrophages from conventional animals. These observations indicate that the microbiota is not essential for the development of Th1 immune responses, but seems to be important for macrophage activation.
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    Immunochemotherapy in american cutaneous leishmaniasis : immunological aspects before and after treatment.
    (2001) Toledo, Vicente de Paulo Coelho Peixoto de; Mayrink, Wilson; Gollob, Kenneth John; Oliveira, Milton Adriano Pelli de; Costa, Carlos Alberto da; Genaro, Odair; Pinto, J. A.; Afonso, Luís Carlos Crocco
    In this study, we evaluated the immune response of patients suffering from cutaneous leishmaniasis treated with two distinct protocols. One group was treated with conventional chemotherapy using pentavalent antimonium salts and the other with immunochemotherapy where a vaccine against cutaneous leishmaniasis was combined with the antimonium salt. Our results show that, although no differences were observed in the necessary time for complete healing of the lesions between the two treatments, peripheral blood mononuclear cells from patients treated by chemotherapy showed smaller lymphoproliferative responses at the end of the treatment than those from patients in the immunochemotherapy group. Furthermore, IFN-production was also different between the two groups. While cells from patients in the chemotherapy group produced more IFN-at the end of treatment, a significant decrease in this cytokine production was associated with healing in the immunochemotherapy group. In addition, IL-10 production was also less intense in this latter group. Finally, an increase in CD8+ -IFN-producing cells was detected in the chemotherapy group. Together these results point to an alternative treatment protocol where healing can be induced with a decreased production of a potentially toxic cytokine.
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    Recrutamento do receptor de adenosina A2B e ativação da via de AMPc- PI3K-ERK1/2 inibem a resposta de células dendríticas infectadas por Leishmania amazonensis.
    (2016) Figueiredo, Amanda Braga de; Afonso, Luís Carlos Crocco; Gonçalves, Teresa Maria Fonseca de Oliveira; Cunha, Rodrigo Pinto dos Santos Antunes da; Brandão, Rogélio Lopes; Oliveira, Milton Adriano Pelli de; Faria, Ana Maria Caetano de; Antonelli, Lis Ribeiro do Valle
    A infecção por Leishmania pode resultar num amplo espectro de manifestações clínicas e a infecção por Leishmania amazonensis é associada a uma deficiência na resposta de linfócitos T específicos para o parasito. Células dendríticas direcionam a diferenciação de linfócitos Th1 que contribuem para o controle da infecção por Leishmania. Em um trabalho anterior, nós mostramos que a infecção por L. amazonensis, mas não por L. braziliensis ou L. major, prejudica a resposta de células dendríticas por um mecanismo dependente do receptor de adenosina A2B. Neste trabalho, nós avaliamos a expressão de receptores de adenosina e os eventos intracelulares ativados a partir do receptor A2B em células dendríticas infectadas, bem como o papel desses eventos na infecção de camundongos por L. amazonensis. Inicialmente, células dendríticas derivadas de células de medula óssea de camundongos C57BL/6J foram infectadas por promastigotas metacíclicas de L. amazonensis, L. braziliensis ou L. major. Imagens obtidas por microscopia de fluorescência mostraram que a infecção por promastigotas metacíclicas de L. amazonensis estimula a redistribuição do receptor A2B para a superfície de células dendríticas infectadas, sem alterar a quantidade total do receptor, avaliada por western blotting, nem a expressão dos receptores de adenosina A1, A2A e A3. A infecção por L. braziliensis, L. major ou promastigotas procíclicas de L. amazonensis não alteram a expressão do receptor A2B em células infectadas. Nossos resultados mostraram, ainda, que a infecção por L. amazonensis estimula a produção de AMPc e a fosforilação de ERK1/2 por mecanismos dependentes do receptor A2B. Além disso, L. amazonensis prejudica a expressão de CD40 e a produção de IL-12p70 por células dendríticas, efeitos independentes de IL-10 e revertidos pela inibição de adenilato ciclase, de PI3K e da fosforilação de ERK1/2. Por fim, camundongos infectados na orelha por L. amazonensis na presença de inibidores do receptor A2B ou das proteínas PI3K ou ERK1/2 desenvolvem lesões menores se comparados a animais controles, mas apenas o bloqueio do receptor A2B é capaz de diminuir o parasitismo tecidual. Concluindo, nós propomos um novo mecanismo utilizado por L. amazonensis (redistribuição do receptor A2B AMPc PI3K ERK1/2) para inibir a ativação de células dendríticas, que parece ser importante para a deficiência na resposta imune observada na infecção por essa espécie de parasito.