AT1 receptor-mediated angiotensin II activation and chemotaxis of T lymphocytes

Angiotensin II (Ang II), a central renin–angiotensin system (RAS) effector molecule, and its receptors, AT1 and AT2, have been shown to be involved in the inflammatory aspects of different diseases, however the cellular mechanisms underlying the regulation of immunity are not fully understood. In this work, using spleen-derived CD4+ and CD8+ T lymphocytes activated in vitro, we tested the influence of Ang II on different aspects of the T cell function, such as activation and adhesion/transmigration through endothelial basal membrane proteins. The addition of 10−8 M Ang II did not change any of the parameters evaluated. However, 10−6 M losartan, an AT1 receptor antagonist: (i) reduced the percentage of CD25+ and CD69+ cells of both subsets; (ii) inhibited adhesion of these cells to fibronectin or laminin by 53% or 76%, respectively and (iii) significantly reduced transmigration through fibronectin or laminin by 57% or 43%, respectively. In addition, 10−6 M captopril, an angiotensin-converting enzyme inhibitor had similar effects to Ang II, however its effects were reverted by exogenous Ang II (10−8 M). None of these responses was modified by 10−7 M PD123319, an AT2 antagonist. These data reinforce the notion of endogenous production of Ang II by T cells, which is important for T cell activation, and adhesion/transmigration induced on interaction with basal membrane proteins, possibly involving AT1 receptor activation. Moreover, AT1 receptor expression is 10-fold higher in activated T lymphocytes compared with naive cells, but AT2 receptor expression did not change after T cell receptor triggering

Human Kinetoplastid Protozoan Infections: Where Are We Going Next?

Submitted by Sandra Infurna ([email protected]) on 2019-02-07T12:49:09Z No. of bitstreams: 1 marisenunes_alexandremorrto_etal_IOC_2018.pdf: 920561 bytes, checksum: 9ed75f91a5b649a7c8fe637233782bf2 (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2019-02-07T12:59:38Z (GMT) No. of bitstreams: 1 marisenunes_alexandremorrto_etal_IOC_2018.pdf: 920561 bytes, checksum: 9ed75f91a5b649a7c8fe637233782bf2 (MD5)Made available in DSpace on 2019-02-07T12:59:38Z (GMT). No. of bitstreams: 1 marisenunes_alexandremorrto_etal_IOC_2018.pdf: 920561 bytes, checksum: 9ed75f91a5b649a7c8fe637233782bf2 (MD5) Previous issue date: 2018Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Instituto de Microbiologia Prof. Paulo de Góes. Departamento de Imunologia. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Instituto de Microbiologia Prof. Paulo de Góes. Departamento de Imunologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunoparasitologia. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Instituto de Microbiologia Prof. Paulo de Góes. Departamento de Imunologia. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Instituto de Microbiologia Prof. Paulo de Góes. Departamento de Imunologia. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Instituto de Microbiologia Prof. Paulo de Góes. Departamento de Imunologia. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Instituto de Microbiologia Prof. Paulo de Góes. Departamento de Imunologia. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Instituto de Microbiologia Prof. Paulo de Góes. Departamento de Imunologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunoparasitologia. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Faculdade de Medicina. Centro de Pesquisa em Tuberculose. Rio de Janeiro, RJ, Brasil.Kinetoplastida trypanosomatidae microorganisms are protozoan parasites exhibiting a developmental stage in the gut of insect vectors and tissues of vertebrate hosts. During the vertebrate infective stages, these parasites alter the differential expression of virulence genes, modifying their biological and antigenic properties in order to subvert the host protective immune responses and establish a persistent infection. One of the hallmarks of kinetoplastid parasites is their evasion mechanisms from host immunity, leading to disease chronification. The diseases caused by kinetoplastid parasites are neglected by the global expenditures in research and development, affecting millions of individuals in the low and middle-income countries located mainly in the tropical and subtropical regions. However, investments made by public and private initiatives have over the past decade leveraged important lines of intervention that if well-integrated to health care programs will likely accelerate disease control initiatives. This review summarizes recent advances in public health care principles, including new drug discoveries and their rational use with chemotherapeutic vaccines, and the implementation of control efforts to spatially mapping the kinetoplastid infections through monitoring of infected individuals in epidemic areas. These approaches should bring us the means to track genetic variation of parasites and drug resistance, integrating this knowledge into effective stewardship programs to prevent vector-borne kinetoplastid infections in areas at risk of disease spreading

Ecological aspects of American cutaneous leishmaniasis: 8. assessment on enzootic activity of Leishmania (V.) braziliensis, in forest and peridomicile environments of the Ribeira Valley region, São Paulo State, Brazil

The evidence of mucocutaneous leishmaniasis transmission in the non-forest environment in the Ribeira Valley region, São Paulo, Brazil, has made this epidemiologic four years' study possible, viewing the enzootic activity of L. (V.) braziliensis. Furthermore, the natural infection in small mammals and the domestic dog population has been completed in collecting of phlebotomine sandflies in the forest and peridomiciliar environments. Positive test-results have only been found in resident dogs (Canis familiaris) with a rate of 5.6 and 2.4% for serological and parasitological test respectively. Among silvatic and synanthropic rodents collected, Oryzomys (Olygoryzomys) and Rattus rattus are preeminent having both been collected in equal proportions, in peridomiciliar environment. The sandfly Lutzomyia intermedia has contributed only with 166 feminine specimens due to insecticide (DDT) application on and in the human and domestic habitations. From the general epidemiologic standpoint the fragile L. (V.) braziliensis cycle in the unforested areas as well as the canine and small mammals roles as a domiciliar infection source are discussed, and their potencial in the dispersion of this parasite in the researched area is analysed too.A evidência da transmissão extraflorestal da leishmaniose cutâneo-mucosa na região do Vale do Ribeira ensejou o presente estudo epidemiológico prospectivo, visando avaliar a atividade enzoótica de L. (V.) braziliensis. A pesquisa paratisológica da infecção natural em pequenos mamíferos e população canina foi complementada com o teste de imunofluorescência indireta (IFI) para cães e captura de flebotomíneos em ambiente florestal e peridomiciliar. A positividade para o teste sorológico e exame parasitológico somente foi observada para cães residentes e com taxas de 5,6 e 2,4%, respectivamente. Entre animais silvestres e sinantrópicos capturados, destacam-se os pertencentes a Oryzomys (Oligoryzomys) e Rattus rattus, ambos assinalados em proporções equivalentes (29,3%), em ambiente peridomiciliar. Foram capturados apenas 166 exemplares femininos de Lutzomyia intermedia, fato atribuído à borrifação das habitações humanas e anexos com DDT. No contexto epidemiológico mais amplo, discute-se a fragilidade do ciclo extraflorestal da L. (V.) braziliensis; o papel do cão e de pequenos mamíferos, como fonte de infecção domiciliar, além de analisar o potencial deles na dispersão do parasita na área estudada

Apoptotic lymphocytes treated with IgG from Trypanosoma cruzi infection increase TNF-alpha secretion and reduce parasite replication in macrophages.

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2015-02-09T17:19:35Z No. of bitstreams: 1 Montalvao F Apoptotic...pdf: 863295 bytes, checksum: d03a35f95c14528a92900489c246a968 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2015-02-09T17:19:51Z (GMT) No. of bitstreams: 1 Montalvao F Apoptotic...pdf: 863295 bytes, checksum: d03a35f95c14528a92900489c246a968 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2015-02-09T17:40:06Z (GMT) No. of bitstreams: 1 Montalvao F Apoptotic...pdf: 863295 bytes, checksum: d03a35f95c14528a92900489c246a968 (MD5)Made available in DSpace on 2015-02-09T17:40:06Z (GMT). No. of bitstreams: 1 Montalvao F Apoptotic...pdf: 863295 bytes, checksum: d03a35f95c14528a92900489c246a968 (MD5) Previous issue date: 2010Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, BrasilUniversidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, BrasilUniversidade Federal Fluminense. Instituto Biomédico. Niterói, RJ, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, BrasilUniversidade Federal Fluminense. Instituto de Biologia. Niterói, RJ, BrasilUniversidade Federal do Rio de Janeiro. Instituto de Ciências Biomédicas. Rio de Janeiro, RJ, BrasilUniversidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil / Instituto Nacional de Saúde e Ambiente na Região Amazônica. Conselho Nacional de Desenvolvimento Científico e Tecnológico. Amazonas, MA, BrasilFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, BrasilUniversidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil / Instituto Nacional de Saúde e Ambiente na Região Amazônica. Conselho Nacional de Desenvolvimento Científico e Tecnológico. Amazonas, MA, BrasilPhagocytic removal of apoptotic lymphocytes exacerbates replication of Trypanosoma cruzi in macrophages. We investigated the presence of Ab against apoptotic lymphocytes in T. cruzi infection and the role of these Ab in parasite replication. Both control and chagasic serum contained IgG Ab that opsonized apoptotic lymphocytes. Treatment of apoptotic lymphocytes with purified IgG from chagasic, but not control serum, reduced T. cruzi replication in macrophages. The protective effect of chagasic IgG depended on Fcgamma receptors, as demonstrated by the requirement for the intact Fc portion of IgG, and the effect could be abrogated by treating macrophages with an anti-CD16/CD32 Fab fragment. Chagasic IgG displayed increased reactivity against a subset of apoptotic cell Ag, as measured by flow cytometry and immunoblot analyses. Apoptotic lymphocytes treated with chagasic IgG, but not control IgG, increased production of TNF-alpha, while decreasing production of TGF-beta1 by infected macrophages. Increased control of parasite replication required TNF-alpha production. Previous immunization with apoptotic cells or injection of apoptotic cells opsonized with chagasic IgG reduced parasitemia in infected mice. These results indicate that Ab raised against apoptotic cells could play a protective role in control of T. cruzi replication by macrophages

Caspase inhibition reduces lymphocyte apoptosis and improves host immune responses to Trypanosoma cruzi infection

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2015-04-22T17:51:30Z No. of bitstreams: 1 Silva E M Caspase inhibition....pdf: 353519 bytes, checksum: 68b3cc8f4df343863de5c4a9370a4777 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2015-04-22T18:34:19Z (GMT) No. of bitstreams: 1 Silva E M Caspase inhibition....pdf: 353519 bytes, checksum: 68b3cc8f4df343863de5c4a9370a4777 (MD5)Made available in DSpace on 2015-04-22T18:34:19Z (GMT). No. of bitstreams: 1 Silva E M Caspase inhibition....pdf: 353519 bytes, checksum: 68b3cc8f4df343863de5c4a9370a4777 (MD5) Previous issue date: 2007Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil.In experimental Chagas' disease, lymphocytes from mice infected with Trypanosoma cruzi show increased apoptosis in vivo and in vitro. Treatment with a pan-caspase blocker peptide inhibited expression of the active form of effector caspase-3 in vitro and rescued both B and T cells from cell death. Injection of the caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethyl ketone, but not a control peptide, reduced parasitemia and lymphocyte apoptosis in T. cruzi-infected mice. Moreover, treatment with caspase inhibitor throughout acute infection increased the absolute numbers of B and T cells in the spleen and lymph nodes, without affecting cell infiltrates in the heart. Following treatment, we found increased accumulation of memory/activated CD4 and CD8 T cells, and secretion of IFN-gamma by splenocytes stimulated with T. cruzi antigens. Caspase inhibition in the course of infection reduced the intracellular load of parasites in peritoneal macrophages, and increased the production of TNF-alpha and nitric oxide upon activation in vitro. Our results indicate that inhibition of caspases with a pan-caspase blocker peptide improves protective type-1 immune responses to T. cruzi infection. We suggest that mechanisms of apoptosis are potential therapeutic targets in Chagas' disease

Turnover of neutrophils mediated by Fas ligand drives Leishmania major infection.

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2015-02-10T13:44:26Z No. of bitstreams: 1 Ribeiro-Gomes FL Turnover...pdf: 2439307 bytes, checksum: 63344954ef36fc4b33455b01fa48f302 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2015-02-10T13:44:35Z (GMT) No. of bitstreams: 1 Ribeiro-Gomes FL Turnover...pdf: 2439307 bytes, checksum: 63344954ef36fc4b33455b01fa48f302 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2015-02-10T13:55:47Z (GMT) No. of bitstreams: 1 Ribeiro-Gomes FL Turnover...pdf: 2439307 bytes, checksum: 63344954ef36fc4b33455b01fa48f302 (MD5)Made available in DSpace on 2015-02-10T13:55:47Z (GMT). No. of bitstreams: 1 Ribeiro-Gomes FL Turnover...pdf: 2439307 bytes, checksum: 63344954ef36fc4b33455b01fa48f302 (MD5) Previous issue date: 2005Federal University of Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, BrasilFederal University of Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, BrasilFederal University of Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, BrasilUniversity of São Paulo. Instituto de Ciências Biomédicas. São Paulo, SP, BrasilFederal University of Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, BrasilApoptosis mediated by Fas ligand (FasL) initiates inflammation characterized by neutrophilic infiltration. Neutrophils undergo apoptosis and are ingested by macrophages. Clearance of dead neutrophils leads to prostaglandin- and transforming growth factor-beta-dependent replication of Leishmania major in macrophages from susceptible mice. How L. major induces neutrophil turnover in a physiological setting is unknown. We show that BALB/c FasL-sufficient mice are more susceptible to L. major infection than are FasL-deficient mice. FasL promotes the apoptosis of infected resident macrophages and attracts neutrophils. Furthermore, FasL-sufficient neutrophils exacerbate L. major replication in macrophages, whereas FasL-deficient neutrophils induce parasite killing. These contrasting effects are due to delaying apoptosis and the clearance of FasL-deficient neutrophils. The transfer of neutrophils exacerbates infection in FasL-sufficient mice but reduces infection in FasL-deficient mice. Depletion of neutrophils abolishes the susceptibility of FasL-sufficient mice. These data illustrate a deleterious role of the FasL-mediated turnover of neutrophils on L. major infection

Canine Macrophage DH82 Cell Line As a Model to Study Susceptibility to Trypanosoma cruzi Infection

Submitted by Sandra Infurna ([email protected]) on 2017-07-05T13:58:03Z No. of bitstreams: 1 marise_nunes_etal_IOC_2017.pdf: 1246095 bytes, checksum: 548f464ca2e48448d7a0f90ad7b62711 (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2017-07-05T14:12:11Z (GMT) No. of bitstreams: 1 marise_nunes_etal_IOC_2017.pdf: 1246095 bytes, checksum: 548f464ca2e48448d7a0f90ad7b62711 (MD5)Made available in DSpace on 2017-07-05T14:12:11Z (GMT). No. of bitstreams: 1 marise_nunes_etal_IOC_2017.pdf: 1246095 bytes, checksum: 548f464ca2e48448d7a0f90ad7b62711 (MD5) Previous issue date: 2017Universidade Federal Rural do Rio de Janeiro. Instituto de Veterinária. Seropédica, RJ, Brasil.Universidade Federal Rural do Rio de Janeiro. Instituto de Veterinária. Seropédica, RJ, Brasil.Universidade Federal Rural do Rio de Janeiro. Instituto de Veterinária. Seropédica, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ. Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil.Universidade Federal Rural do Rio de Janeiro. Instituto de Veterinária. Seropédica, RJ, Brasil.Trypanosoma cruzi is an obligatory intracellular protozoan parasite, and it is the etiological agent of Chagas' disease that is endemic in the Americas. In addition to humans, a wide spectrum of mammals can be infected by T. cruzi, including dogs. Dogs develop acute and chronic disease, similar to human infection. T. cruzi can infect almost all cell types and after cell invasion, the metacyclics trypomastigotes localize in the cytoplasm, where they transform into amastigotes, the replicative form of T. cruzi in mammals. After amastigote multiplication and differentiation, parasites lyse host cells and spread through the body by blood circulation. In this work, we evaluated the in vitro ability of T. cruzi to infect a canine macrophage cell line DH82 compared with RAW264.7, a murine tissue culture macrophage. Our results have shown that the T. cruzi is able to infect, replicate and differentiate in DH82 cell line. We observed that following treatment with LPS and IFN-γ DH82 cells were more resistant to infection and that resistance was not related reactive oxygen species production in our system. In this study, we also found that DH82 cells became more susceptible to T. cruzi infection when cocultured with apoptotic cells. The analysis of cytokine production has showed elevated levels of the TGF-β, IL-10, and TNF-α produced by T. cruzi-infected canine macrophages. Additionally, we demonstrated a reduced expression of the MHC class II and CD80 by infected DH82 cell line

Kinetoplastid membrane protein-11 exacerbates infection with Leishmania amazonensis in murine macrophages

In Leishmania amazonensis, kinetoplastid membrane protein-11 (KMP-11) expression increases during metacyclogenesis and is higher in amastigotes than in promastigotes, suggesting a role for this protein in the infection of the mammalian host. We show that the addition of KMP-11 exacerbates L. amazonensis infection in peritoneal macrophages from BALB/c mice by increasing interleukin (IL)-10 secretion and arginase activity while reducing nitric oxide (NO) production. The doses of KMP-11, the IL-10 levels and the intracellular amastigote loads were strongly, positively and significantly correlated. The increase in parasite load induced by KMP-11 was inhibited by anti-KMP-11 or anti-IL-10 neutralising antibodies, but not by isotype controls. The neutralising antibodies, but not the isotype controls, were also able to significantly decrease the parasite load in macrophages cultured without the addition of KMP-11, demonstrating that KMP-11-induced exacerbation of the infection is not dependent on the addition of exogenous KMP-11 and that the protein naturally expressed by the parasite is able to promote it. In this study, the exacerbating effect of KMP-11 on macrophage infection with Leishmania is for the first time demonstrated, implicating it as a virulence factor in L. amazonensis. The stimulation of IL-10 production and arginase activity and the inhibition of NO synthesis are likely involved in this effect