Trypanosoma cruzi Infection Induces Cellular Stress Response and Senescence-Like Phenotype in Murine Fibroblasts

Trypanosoma cruzi infects and replicates within a wide variety of immune and non-immune cells. Here, we investigated early cellular responses induced in NIH-3T3 fibroblasts upon infection with trypomastigote forms of T. cruzi. We show that fibroblasts were susceptible to T. cruzi infection and started to release trypomastigotes to the culture medium after 4 days of infection. Also, we found that T. cruzi infection reduced the number of fibroblasts in 3-day cell cultures, by altering fibroblast proliferation. Infected fibroblasts displayed distinctive phenotypic alterations, including enlarged and flattened morphology with a nuclei accumulation of senescence-associated heterochromatin foci. In addition, infection induced an overexpression of the enzyme senescence-associated β-galactosidase (SA-β-gal), an activation marker of the cellular senescence program, as well as the production of cytokines and chemokines involved with the senescence-associated secretory phenotype (SASP) such as IL-6, TNF-α, IL-1β, and MCP-1. Infected fibroblasts released increased amounts of stress-associated factors nitric oxide (NO) and reactive oxygen species (ROS), and the treatment with antioxidants deferoxamine (DFO) and N-acetylcysteine reduced ROS generation, secretion of SASP-related cytokine IL-6, SA-β-gal activity, and parasite load by infected fibroblasts. Taken together, our data suggest that T. cruzi infection triggers a rapid cellular stress response followed by induction of a senescent-like phenotype in NIH-3T3 fibroblasts, enabling them to act as reservoirs of parasites during the early stages of the Chagas disease

The central role of Fas-ligand cell signaling in inflammatory lung diseases.

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2015-02-10T14:11:37Z No. of bitstreams: 1 DosReis GA The central...pdf: 1398350 bytes, checksum: 38fc272d7e226f14c4c4eb70ec8b5764 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2015-02-10T14:11:46Z (GMT) No. of bitstreams: 1 DosReis GA The central...pdf: 1398350 bytes, checksum: 38fc272d7e226f14c4c4eb70ec8b5764 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2015-02-10T14:22:32Z (GMT) No. of bitstreams: 1 DosReis GA The central...pdf: 1398350 bytes, checksum: 38fc272d7e226f14c4c4eb70ec8b5764 (MD5)Made available in DSpace on 2015-02-10T14:22:32Z (GMT). No. of bitstreams: 1 DosReis GA The central...pdf: 1398350 bytes, checksum: 38fc272d7e226f14c4c4eb70ec8b5764 (MD5) Previous issue date: 2004Federal 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, BrasilFederal University of Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, BrasilFollowing inflammation and injury in the lung, loss of epithelial cell precursors could determine the balance between tissue regeneration and fibrosis. This review discusses evidence that proapoptotic Fas-Fas ligand (FasL) signaling plays a central role in pulmonary inflammation, injury and fibrosis. FasL signaling induces inflammatory apoptosis in epithelial cells and alveolar macrophages, with concomitant IL-1 beta and chemokine release, leading to neutrophil infiltration. FasL signaling plays a critical role in models of acute lung injury, idiopathic pulmonary fibrosis and silicosis; blockade of Fas-FasL interactions either prevents or attenuates pulmonary inflammation and fibrosis. Serologic and immunohistochemical studies in patients support a major pathogenic role of Fas and FasL molecules in inflammatory lung diseases. Identification of the pathogenic role of FasL could facilitate the discovery of more effective treatments for currently untreatable inflammatory lung disease

Innate Immunity to Leishmania Infection: Within Phagocytes

Infection by Leishmania takes place in the context of inflammation and tissue repair. Besides tissue resident macrophages, inflammatory macrophages and neutrophils are recruited to the infection site and serve both as host cells and as effectors against infection. Recent studies suggest additional important roles for monocytes and dendritic cells. This paper addresses recent experimental findings regarding the regulation of Leishmania major infection by these major phagocyte populations. In addition, the role of IL-4 on dendritic cells and monocytes is discussed

Degranulating Neutrophils Promote Leukotriene B4 Production by Infected Macrophages To Kill Leishmania amazonensis Parasites

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2016-08-02T18:27:42Z No. of bitstreams: 1 Tavares Degranulation... 2016.pdf: 1492596 bytes, checksum: a4024e14fec7c89c81c19a5f752e5411 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2016-08-02T18:42:20Z (GMT) No. of bitstreams: 1 Tavares Degranulation... 2016.pdf: 1492596 bytes, checksum: a4024e14fec7c89c81c19a5f752e5411 (MD5)Made available in DSpace on 2016-08-02T18:42:20Z (GMT). No. of bitstreams: 1 Tavares Degranulation... 2016.pdf: 1492596 bytes, checksum: a4024e14fec7c89c81c19a5f752e5411 (MD5) Previous issue date: 2016-02-15Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, Brasil / Instituto de Investigação em Imunologia. São Paulo, SP, BrasilUniversidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, Brasil / Instituto de Investigação em Imunologia. São Paulo, SP, BrasilNeutrophils mediate early responses against pathogens, and they become activated during endothelial transmigration toward the inflammatory site. In the current study, human neutrophils were activated in vitro with immobilized extracellular matrix proteins, such as fibronectin (FN), collagen, and laminin. Neutrophil activation by FN, but not other extracellular matrix proteins, induces the release of the granules' contents, measured as matrix metalloproteinase 9 and neutrophil elastase activity in culture supernatant, as well as reactive oxygen species production. Upon contact with Leishmania amazonensis-infected macrophages, these FN-activated neutrophils reduce the parasite burden through a mechanism independent of cell contact. The release of granule proteases, such as myeloperoxidase, neutrophil elastase, and matrix metalloproteinase 9, activates macrophages through TLRs, leading to the production of inflammatory mediators, TNF-α and leukotriene B4 (LTB4), which are involved in parasite killing by infected macrophages. The pharmacological inhibition of degranulation reverted this effect, abolishing LTB4 and TNF production. Together, these results suggest that FN-driven degranulation of neutrophils induces the production of LTB4 and TNF by infected macrophages, leading to the control of Leishmania infection

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

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

Antibody Repertoires Identify β-Tubulin as a Host Protective Parasite Antigen in Mice Infected With Trypanosoma cruzi

Few studies investigate the major protein antigens targeted by the antibody diversity of infected mice with Trypanosoma cruzi. To detect global IgG antibody specificities, sera from infected mice were immunoblotted against whole T. cruzi extracts. By proteomic analysis, we were able to identify the most immunogenic T. cruzi proteins. We identified three major antigens as pyruvate phosphate dikinase, Hsp-85, and β-tubulin. The major protein band recognized by host IgG was T. cruzi β-tubulin. The T. cruzi β-tubulin gene was cloned, expressed in E. coli, and recombinant T. cruzi β-tubulin was obtained. Infection increased IgG reactivity against recombinant T. cruzi β-tubulin. A single immunization of mice with recombinant T. cruzi β-tubulin increased specific IgG reactivity and induced protection against T. cruzi infection. These results indicate that repertoire analysis is a valid approach to identify antigens for vaccines against Chagas disease

Influence of composition and continuous casting parameters on the cracking of b-microalloyed high Mn steel grades

B-1 cells can be differentiated from B-2 cells because they are predominantly located in the peritoneal and pleural cavities and have distinct phenotypic patterns and activation properties. A mononuclear phagocyte derived from B-1 cells (B-1CDP) has been described. As the B-1CDP cells migrate to inflammatory/infectious sites and exhibit phagocytic capacity, the microbicidal ability of these cells was investigated using the Leishmania major infection model in vitro. The data obtained in this study demonstrate that B-1CDP cells are more susceptible to infection than peritoneal macrophages, since B-1CDP cells have a higher number of intracellular amastigotes forms and consequently release a larger number of promastigotes. Exacerbated infection by L. major required lipid bodies/PGE2 and IL-10 by B-1CDP cells. Both infection and the production of IL-10 were decreased when PGE2 production was blocked by NSAIDs. The involvement of IL-10 in this mechanism was confirmed, since B-1CDP cells from IL-10 KO mice are more competent to control L. major infection than cells from wild type mice. These findings further characterize the B-1CDP cells as an important mononuclear phagocyte that plays a previously unrecognized role in host responses to L. major infection, most likely via PGE2-driven production of IL-10

Involvement of the capsular GalXM-induced IL-17 cytokine in the control of Cryptococcus neoformans infection

Submitted by Sandra Infurna ([email protected]) on 2019-01-22T15:31:03Z No. of bitstreams: 1 marisep_nunes_etal_IOC_2018.pdf: 1948055 bytes, checksum: aa4c6dd74bde818694451ae1b63ffc83 (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2019-01-22T15:42:06Z (GMT) No. of bitstreams: 1 marisep_nunes_etal_IOC_2018.pdf: 1948055 bytes, checksum: aa4c6dd74bde818694451ae1b63ffc83 (MD5)Made available in DSpace on 2019-01-22T15:42:06Z (GMT). No. of bitstreams: 1 marisep_nunes_etal_IOC_2018.pdf: 1948055 bytes, checksum: aa4c6dd74bde818694451ae1b63ffc83 (MD5) Previous issue date: 2018Universidade 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. Instituto Oswaldo Cruz. Laboratório de Imunoparasitologia. 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. Instituto Oswaldo Cruz. Laboratório de Imunoparasitologia. Rio de Janeiro, RJ. Brasil / Universidade Federal do Rio de Janeiro. Faculdade de Medicina. Rio de Janeiro, 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 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.Cryptococcus neoformans is an opportunistic fungus that can cause lethal brain infections in immunosuppressed individuals. Infection usually occurs via the inhalation of a spore or desiccated yeast which can then disseminate from the lung to the brain and other tissues. Dissemination and disease is largely influence by the production of copious amounts of cryptococcal polysaccharides, both which are secreted to the extracellular environment or assembled into a thick capsule surrounding the cell body. There are two important polysaccharides: glucuronoxylomannan (GXM) and galactoxylomannan, also called as glucuronoxylomanogalactan (GXMGal or GalXM). Although GXM is more abundant, GalXM has a more potent modulatory effect. In the present study, we show that GalXM is a potent activator of murine dendritic cells, and when co-cultured with T cells, induces a Th17 cytokine response. We also demonstrated that treating mice with GalXM prior to infection with C. neoformans protects from infection, and this phenomenon is dependent on IL-6 and IL-17. These findings help us understand the immune biology of capsular polysaccharides in fungal pathogenesis