The Interleukin-17 (IL-17) Puzzle in Chagas’ Disease

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2018-03-20T12:57:40Z No. of bitstreams: 1 Mengel J The Interleukin-17 (IL-17) puzzle ....pdf: 416819 bytes, checksum: 341236ff108c0829c4429bb88a1cddcf (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2018-03-20T13:11:33Z (GMT) No. of bitstreams: 1 Mengel J The Interleukin-17 (IL-17) puzzle ....pdf: 416819 bytes, checksum: 341236ff108c0829c4429bb88a1cddcf (MD5)Made available in DSpace on 2018-03-20T13:11:33Z (GMT). No. of bitstreams: 1 Mengel J The Interleukin-17 (IL-17) puzzle ....pdf: 416819 bytes, checksum: 341236ff108c0829c4429bb88a1cddcf (MD5) Previous issue date: 2017Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunologia Clínica. Rio de Janeiro, RJ, Brasil / Faculty of Medicine of Petrópolis. Petrópolis, RJ, BrazilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, BrasilIn this article, we discuss an alternative explanation for the fact that the production and plasma levels of IL-17 are diminished in patients chronically infected with Trypanosoma cruzi, suffering from congestive heart failure. This alternate hypothesis considers the inhibitory pharmacological action of digoxin, a drug commonly used to treat heart failure. We believe this is a significant point to be further studied as IL-17 was initially considered to be heart-protective. Therefore, our argument has profound therapeutic implication

The ACE inhibitors enalapril and captopril modulate cytokine responses in Balb/c and C57Bl/6 normal mice and increase CD4(+)CD103(+)CD25(negative) splenic T cell numbers.

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2015-06-17T18:30:14Z No. of bitstreams: 1 Albuquerque D The ace inhibitors....pdf: 598548 bytes, checksum: 83147fecb282449cb85445c07f81bde3 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2015-06-17T18:44:21Z (GMT) No. of bitstreams: 1 Albuquerque D The ace inhibitors....pdf: 598548 bytes, checksum: 83147fecb282449cb85445c07f81bde3 (MD5)Made available in DSpace on 2015-06-17T18:44:21Z (GMT). No. of bitstreams: 1 Albuquerque D The ace inhibitors....pdf: 598548 bytes, checksum: 83147fecb282449cb85445c07f81bde3 (MD5) Previous issue date: 2010Federal University of Mato Grosso. Faculty of Medicine. Department of Basic Health Science. Cuiabá, MG, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilUCLA David Geffen School of Medicine. Division of Rheumatology. Los Angeles, CA, USAIncreasing evidence implies beneficial effects of angiotensin-converting enzyme (ACE) inhibitors beyond those of their original indications to control hypertension. One of the most attractive non-hemodynamic properties of ACE inhibitors is their ability to regulate cytokine production. The mechanism(s) underlying the role of ACE inhibitors on cytokine synthesis are not well understood but they have traditionally been attributed to the inhibition of angiotensin (Ang) II formation. In fact, it has been extensively demonstrated that ACE inhibitors decrease Ang II-induced production of proinflammatory cytokines and chemokines. However, it is not well described if inhibition of endogenous Ang II generation by ACE inhibitors modulates systemic cytokine production in mice. To verify that, in this work, we investigated the effects of treatment with the ACE inhibitors enalapril and captopril on cytokine synthesis in C57Bl/6 and Balb/c mice. Our results show that enalapril up regulates IL-10 produced by splenocytes from Balb/c and C57Bl/6 mice and captopril increased it only in Balb/c mice. Furthermore, CD4(+)CD103(+) presented increased IL-10 production after enalapril treatment. Enalapril as well as captopril short-term treatment enhanced IL-2 synthesis in Balb/c mice. Besides, enhanced IL-2 and IL-10 levels correlates with increased CD4(+)CD103(+)CD25(negative) T cells numbers in spleens from enalapril-treated mic

NK1.1 cells are required to control T cell hyperactivity during Trypanosoma cruzi infection.

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2015-06-18T12:17:42Z No. of bitstreams: 1 Cardillo F NK! 1 are required....pdf: 1290378 bytes, checksum: 13c8e37095d5f8e755e95fbabbf02a6b (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2015-06-18T13:03:27Z (GMT) No. of bitstreams: 1 Cardillo F NK! 1 are required....pdf: 1290378 bytes, checksum: 13c8e37095d5f8e755e95fbabbf02a6b (MD5)Made available in DSpace on 2015-06-18T13:03:27Z (GMT). No. of bitstreams: 1 Cardillo F NK! 1 are required....pdf: 1290378 bytes, checksum: 13c8e37095d5f8e755e95fbabbf02a6b (MD5) Previous issue date: 2004University of São Paulo. Institute for Biomedical Sciences IV. Department of Immunology. São Paulo, SP, Brasil / University of São Paulo. Department of Clinical Analysis. São Paulo, SP, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratório de Doença Experimental de Chagas, Imunologia Celular e Auto-imunidade. Salvador, BA, BrasilUniversity of São Paulo. Department of Clinical Analysis. São Paulo, SP, BrasilUniversity of São Paulo. Institute for Biomedical Sciences IV. Department of Immunology. São Paulo, SP, BrasilUniversity of São Paulo. Institute for Biomedical Sciences IV. Department of Immunology. São Paulo, SP, Brasil / University of São Paulo. Department of Clinical Analysis. São Paulo, SP, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratório de Doença Experimental de Chagas, Imunologia Celular e Auto-imunidade. Salvador, BA, BrasilBACKGROUND: This study evaluated the regulatory function of NK1.1+ cells during Trypanosoma cruzi infection. MATERIAL/METHODS: Both thymectomized (Tx C57Bl/6) and euthymic C57Bl/6 mice (C57Bl/6) were infected intraperitoneally with the Tulahuen strain. NK1.1+ cells were depleted in vivo by anti-NK1.1 mAb. Spleen cells were analyzed by flow cytometry for the expression of CD44 and CD69 on T cells. Supernatants from splenocytes were used to measure nitrite concentration (quantified by Griess reagent). Interleukin 2 and IFN-gamma levels were determined by ELISA. The protocols used herein were approved by the Institutional Committee for Ethics. Student's t or Kruskal-Wallis tests were applied, as indicated. RESULTS: The number of T cells expressing CD69 increased progressively during T. cruzi infection in NK1.1 cell-depleted C57Bl/6 mice. In spite of an increased early T cell activation during infection, the percentage of CD4+ CD44high T cells did not augment in NK1.1 cell-depleted C57Bl/6 mice compared with untreated C57Bl/6 controls. Serum levels of IFN-gamma in anti-NK1.1-treated mice were higher than in non-depleted animals. Con-A-stimulated spleen cell supernatants from NK1.1 cell-depleted animals contained increased levels of IL-2 and nitric oxide (NO) during early infection. CONCLUSIONS: After the first week of infection, NO overproduction and high levels of IFN-gamma in anti-NK1.1-tre-ated C57Bl/6 mice appeared to be related to susceptibility and hyperactivation of peripheral T cells. Finally, this study suggests a novel regulatory function of NK1.1+ cells during T. cruzi infection. Without NK1.1 cells, T lymphocytes are hyperactivated but do not differentiate to effector/memory T cells in infected C57Bl/6 mice

Scrutinizing the Biomarkers for the Neglected Chagas Disease: How Remarkable!

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2016-12-05T18:56:08Z No. of bitstreams: 1 Pinho RT Scrutinizing the....pdf: 148854 bytes, checksum: bf9437d58b1d18248d90438215e348b1 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2016-12-05T19:20:38Z (GMT) No. of bitstreams: 1 Pinho RT Scrutinizing the....pdf: 148854 bytes, checksum: bf9437d58b1d18248d90438215e348b1 (MD5)Made available in DSpace on 2016-12-05T19:20:38Z (GMT). No. of bitstreams: 1 Pinho RT Scrutinizing the....pdf: 148854 bytes, checksum: bf9437d58b1d18248d90438215e348b1 (MD5) Previous issue date: 2016CNPq-PQ-2 and FAPERJ-JCNE fellowships (PA), and fully supported by PAPES/CNPq/FIOCRUZ and Fundação Octacílio Gualberto, Faculdade de Medicina de Petropolis (FMP-FASE).Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunologia Clínica. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genômica Funcional e Bioinformática. Rio de Janeiro, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunologia Clínica. Rio de Janeiro, RJ, Brasil / Faculdade de Medicina de Petropolis (FMP-FASE). Petrópolis, RJ, BrasilFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunologia Clínica. Rio de Janeiro, RJ, BrasilBiomarkers or biosignature profiles have become accessible over time in population-based studies for Chagas disease. Thus, the identification of consistent and reliable indicators of the diagnosis and prognosis of patients with heart failure might facilitate the prioritization of therapeutic management to those with the highest chance of contracting this disease. The purpose of this paper is to review the recent state and the upcoming trends in biomarkers for human Chagas disease. As an emerging concept, we propose a classification of biomarkers based on plasmatic-, phenotype-, antigenic-, genetic-, and management-related candidates. The available data revisited here reveal the lessons learned thus far and the existing challenges that still lie ahead to enable biomarkers to be employed consistently in risk evaluation for this disease. There is a strong need for biomarker validation, particularly for biomarkers that are specific to the clinical forms of Chagas disease. The current failure to achieve the eradication of the transmission of this disease has produced determination to solve this validation issue. Finally, it would be strategic to develop a wide variety of biomarkers and to test them in both preclinical and clinical trials

Immunity and immune modulation in Trypanosoma cruzi infection

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2017-07-06T12:45:50Z No. of bitstreams: 1 Cardillo F Immunity and immune....pdf: 224612 bytes, checksum: 7e377921fcddb03753651f7aa2215122 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2017-07-06T12:55:35Z (GMT) No. of bitstreams: 1 Cardillo F Immunity and immune....pdf: 224612 bytes, checksum: 7e377921fcddb03753651f7aa2215122 (MD5)Made available in DSpace on 2017-07-06T12:55:35Z (GMT). No. of bitstreams: 1 Cardillo F Immunity and immune....pdf: 224612 bytes, checksum: 7e377921fcddb03753651f7aa2215122 (MD5) Previous issue date: 2015CNPq, PAPES/FIOCRUZ and FOGFMP/FASE. PRZA is granted with CNPq and FAPERJFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunologia Clínica. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunologia Clínica. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunologia Clínica. Rio de Janeiro, RJ, Brasil / Faculty of Medicine of Petropolis. Petrópolis, RJ, BrazilChagas disease is caused by the protozoan Trypanosoma cruzi. The parasite reaches the secondary lymphoid organs, the heart, skeletal muscles, neurons in the intestine and esophagus among other tissues. The disease is characterized by mega syndromes, which may affect the esophagus, the colon and the heart, in about 30% of infected people. The clinical manifestations associated with T. cruzi infection during the chronic phase of the disease are dependent on complex interactions between the parasite and the host tissues, particularly the lymphoid system that may either result in a balanced relationship with no disease or in an unbalanced relationship that follows an inflammatory response to parasite antigens and associated tissues in some of the host organs and/or by an autoimmune response to host antigens. This review discusses the findings that support the notion of an integrated immune response, considering the innate and adaptive arms of the immune system in the control of parasite numbers and also the mechanisms proposed to regulate the immune response in order to tolerate the remaining parasite load, during the chronic phase of infection. This knowledge is fundamental to the understanding of the disease progression and is essential for the development of novel therapies and vaccine strategies

Vg1 gd T cells regulate type-1/type-2 immune responses and participate in the resistance to infection and development of heart inflammation in Trypanosoma cruzi-infected BALB/c mice.

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2014-09-04T16:51:59Z No. of bitstreams: 1 Nomizo A Vg1 gd T cells regulate......pdf: 627769 bytes, checksum: 92918c4b307fdc95f4a92d6956008285 (MD5)Made available in DSpace on 2014-09-04T16:51:59Z (GMT). No. of bitstreams: 1 Nomizo A Vg1 gd T cells regulate......pdf: 627769 bytes, checksum: 92918c4b307fdc95f4a92d6956008285 (MD5) Previous issue date: 2006University of São Paulo. Department of Clinical Analysis, Toxicology and Bromatology. FCFRP. Ribeirão Preto, SP, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, BrasilUniversity of São Paulo. Institute for Biomedical Sciences IV. Department of Immunology. São Paulo, SP, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, BrasilMany different cell populations or lineages participate in the resistance to Trypanosoma cruzi infection. gammadelta T cells may also take part in a network of interactions that lead to control of T. cruzi infection with minimal tissue damage by controlling alphabeta T cell activation, as was previously suggested. However, the gammadelta T cell population is not homogeneous and its functions might vary, depending on T cell receptor usage or distinct stimulatory conditions. In this study, we show that the in vivo depletion of V gamma 1-bearing gammadelta T cells, prior to the infection of BALB/c mice with the Y strain of T. cruzi, induces an increased susceptibility to the infection with lower amounts of IFN-gamma being produced by conventional CD4+ or CD8+ T cells. In addition, the production of IL-4 by spleen T cells in V gamma 1-depleted mice was increased and the production of IL-10 remained unchanged. Since V gamma 1(+) gammadelta T cell depletion diminished the conversion of naive to memory/activated CD4 T cells and the production of IFN-gamma during the acute infection, these cells appear to function as helper cells for conventional CD4+ Th1 cells. Depletion of V gamma 1(+) cells also reduced the infection-induced inflammatory infiltrate in the heart and skeletal muscle. More importantly, V gamma 1(+) cells were required for up-regulation of CD40L in CD4+ and CD8+ T cells during infection. These results show that a subset of gammadelta T cells (V gamma 1(+)), which is an important component of the innate immune response, up-regulates the type 1 arm of the adaptative immune response, during T. cruzi infection

Long-term administration of IgG2a anti-NK1.1 monoclonal antibody ameliorates lupus-like disease in NZB/W mice in spite of an early worsening induced by an IgG2a-dependent BAFF/BLyS production

The role of natural killer (NK) T cells in the development of lupus-like disease in mice is still controversial. We treated NZB/W mice with anti-NK1.1 monoclonal antibodies (mAbs) and our results revealed that administration of either an irrelevant immunoglobulin G2a (IgG2a) mAb or an IgG2a anti-NK1.1 mAb increased the production of anti-dsDNA antibodies in young NZB/W mice. However, the continuous administration of an anti-NK1.1 mAb protected aged NZB/W mice from glomerular injury, leading to prolonged survival and stabilization of the proteinuria. Conversely, the administration of the control IgG2a mAb led to an aggravation of the lupus-like disease. Augmented titres of anti-dsDNA in NZB/W mice, upon IgG2a administration, correlated with the production of BAFF/BLyS by dendritic, B and T cells. Treatment with an anti-NK1.1 mAb reduced the levels of interleukin-16, produced by T cells, in spleen cell culture supernatants from aged NZB/W. Adoptive transfer of NK T cells from aged to young NZB/W accelerated the production of anti-dsDNA in recipient NZB/W mice, suggesting that NK T cells from aged NZB/W are endowed with a B-cell helper activity. In vitro studies, using purified NK T cells from aged NZB/W, showed that these cells provided helper B-cell activity for the production of anti-dsDNA. We concluded that NK T cells are involved in the progression of lupus-like disease in mature NZB/W mice and that immunoglobulin of the IgG2a isotype has an enhancing effect on antibody synthesis due to the induction of BAFF/BLyS, and therefore have a deleterious effect in the NZB/W mouse physiology

Experimental Parasitology

Texto completo: acesso restrito. p.201–205CBA/J mice are resistant to Leishmania major and susceptible to Leishmania amazonensis. Early events determine infection outcome. Until now, PIV (in vitro priming) immune response to L. amazonensis has not been assessed. Herein, we have shown that compared to L. major, L. amazonensis induced higher parasite burden associated to similar IL-4, IFN-γ, and TNF-α mRNA expressions and IFN-γ and IL-10 levels. Although similar amounts of IL-10 were detected, the frequency of intracellular IL-10 positive B cells was enhanced in spleen cells stimulated with anti-CD3/anti-CD28, or anti-CD3/anti-CD28 and L. amazonensis, compared to L. major-stimulation. Interestingly, IL-10- producing B cells were reduced in response to anti-CD3/anti-CD28 stimulation combined with L. major compared to the other groups. L. amazonensis may favor T regulatory cell development, since 40% of all the CD4+CD25+ were CD25high cells. These data suggest that in PIV, susceptibility to L. amazonensis is not related to Th cell polarization, but to the presence and activity of regulatory T and B cells

Administration of a nondepleting anti-CD25 monoclonal antibody reduces disease severity in mice infected with Trypanosoma cruzi

Made available in DSpace on 2015-04-06T17:18:17Z (GMT). No. of bitstreams: 2 j_niheietal_centrogoncalomuniz_2014.pdf: 525297 bytes, checksum: 159896f015781692d1c6cd8ace42e9ac (MD5) license.txt: 1914 bytes, checksum: 7d48279ffeed55da8dfe2f8e81f3b81f (MD5) Previous issue date: 2014Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Muniz. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Muniz. Salvador,BA, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil. Faculdade de Medicina de Petrópolis - FMP/FASE. Petrópolis, RJ, Brasil.The role of CD25+ regulatory T cells during the course of Trypanosoma cruzi infection has been previously analyzed, and the bulk of results have shown a limited role for this T cell subpopulation. In this study, we have used an IgM, nondepleting monoclonal antibody (mAb) aiming at blocking interleukin (IL)-2 activity on CD25+ T cells. The administration of this antibody 10 days before infection increased the resistance of outbred Swiss mice to the Colombian strain of T. cruzi. Anti-CD25-treated mice had lower parasitemia and augmented numbers of effector memory T cells. In addition, these animals showed higher numbers of splenic T cells secreting IFN-γ and TNF-α, both cytokines described to be involved in the resistance to T. cruzi infection. The same treatment also increased the numbers of splenic T cells that produced homeostatic and regulatory cytokines, such as IL-2 and IL-10, and CD4+CD25+ T cells. The administration of nondepleting anti-CD25 mAb at the beginning of the chronic phase, when parasites were cleared from the blood, halted the inflammatory process in the heart, without any signs of infection reactivation. These results indicate that nondepleting anti-CD25 monoclonal antibodies may be useful to treat chronic Chagas’ disease

Bacillus Calmette–Guérin Immunotherapy for Cancer

Bacillus Calmette–Guérin (BCG), an attenuated vaccine from Mycobacterium bovis, was initially developed as an agent for vaccination against tuberculosis. BCG proved to be the first successful immunotherapy against established human bladder cancer and other neoplasms. The use of BCG has been shown to induce a long-lasting antitumor response over all other forms of treatment against intermediate, non-invasive muscle bladder cancer Several types of tumors may now be treated by releasing the immune response through the blockade of checkpoint inhibitory molecules, such as CTLA-4 and PD-1. In addition, Toll-Like Receptor (TLR) agonists and BCG are used to potentiate the immune response against tumors. Studies concerning TLR-ligands combined with BCG to treat melanoma have demonstrated efficacy in treating mice and patients This review addresses several interventions using BCG on neoplasms, such as Leukemia, Bladder Cancer, Lung Cancer, and Melanoma, describing treatments and antitumor responses promoted by this attenuated bacillus. Of essential importance, BCG is described recently to participate in an adequate microbiome, establishing an effective response during cell-target therapy when combined with anti-PD-1 antibody, which stimulates T cell responses against the melanoma. Finally, trained immunity is discussed, and reprogramming events to shape innate immune responses are addressed