Estudo morfológico in situ da resposta imuno-inflamatória na tuberculose pulmonar humana

Submitted by Repositório Arca ([email protected]) on 2019-07-17T17:05:42Z No. of bitstreams: 1 license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2019-07-18T17:44:43Z (GMT) No. of bitstreams: 2 Almerio Liborio Lopes de - Noronha Estudo...2003.pdf: 23200879 bytes, checksum: 9b21399550af11e6784310c655f7b242 (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5)Made available in DSpace on 2019-07-18T17:44:43Z (GMT). No. of bitstreams: 2 Almerio Liborio Lopes de - Noronha Estudo...2003.pdf: 23200879 bytes, checksum: 9b21399550af11e6784310c655f7b242 (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2003FAPESBUniversidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil.A tuberculose é uma doença antiga responsável pela morte de milhares de pessoas e que até hoje em dia não foi controlada. As alterações causadas pelo bacilo no organismo bem como os mecanismos imunológicos de defesa ainda estão sob intensa investigação pelo mundo. Apesar do volume de trabalhos científicos muito pouco se estuda em seres humanos com material de necrópsias. O objetivo do presente estudo é fazer uma correlação morfológica entre as lesões observadas em pacientes com tuberculose pulmonar, HIV + / HIV - contribuindo para o entendimento das interações entre células de defesa, bacilo e citocinas na resposta imuno-inflamatória que se monta, elucidando possíveis variações morfológicas destas lesões e os seus significados funcionais. Foram analisados ao microscópio óptico cortes histológicos de pacientes autopsiados no (HUPES) entre 1995 e 2001 com diagnóstico anátomo patológico de tuberculose pulmonar. O enfoque principal foram os granulomas ou lesões observadas nos cortes histológicos de pulmões dos casos selecionados onde além do H/E e Ziehl- Niels en foram feitas marcações imunohistoquimicas para IFN-y, TNF-a e TGF-p. Os casos de cada grupo foram cuidadosamente selecionados excluindo-se aqueles que tivessem outra doença pulmonar que não tuberculose para evitar resultados falso positivos ou falso negativos pela presença de mais de um agente etiológico. Os resultados foram analisados por meio de tabelas algorítmicas vista por pelo menos três observadores onde foi feita a análise dos parâmetros morfológicos como a formação e modulação dos granulomas, a arquitetura e composição celular dos mesmos assim como a presença e extensão da necrose. Foi feito também uma avaliação das citocinas. Os resultados foram comparados e uma média dos valores foi utilizada no estudo. O grupo HIV + mostrou granulomas mal formados, com pouca ou nenhuma modulação, com extensas áreas de necrose e ainda com uma composição celular diferente onde predominam polimorfonucleares. No grupo HIV - o padrão de resposta imuno-inflamatória foi bastante diferente sendo observados granulomas bem formados com arquitetura preservada, variável quantidade de necrose e composto predominantemente por células mononucleares e com a presença de células epitelióides e células gigantes. Foram observadas também diferenças nos perfis de citocinas nas lesões que fogem ao que está descrito na literatura. Portanto existem padrões morfológicos diferentes para a tuberculose pulmonar humana quando se comparam pacientes HIV +/ HIV - e estas variações estão intimamente relacionadas ao estado da imunidade celular destes pacientes.Tuberculosis is an old existing disease, responsible for thousands’ deaths and until nowadays has not been controlled. The changes caused in the organism by the bacillus as well as complete immunologycal defense’s mechanisms are still under investigation. Although there are many in vitro’s scientific publications, we can rarely find works about human beings from the aspect of necropsy purely. The purpose of this study is making a morphologic relation between observed injuries in patients with pulmonary tuberculosis, HIV + / HIV - contributing for the understanding of the interaction between defense’s cells, bacillus and cytokines resulted by the immuno-inflammatory response, demonstrating possible morphologic variations of these injuries and its functional meanings. Histological sections from autopsied patients presenting anatomy pathologic diagnosis in HUPES from 1995 to 2001, were analyzed by optical microscopy. The granulomas or injuries observed in lung’s histological sections of cases selected that were submitted to H/E, Ziehl- Nielsen and immunohistochemistry reactions to IFN-y, TNF-a and TGF-p were considered the focus of this study. Each group was carefully selected, excluding those cases that presented any other pulmonary disease rather than tuberculosis, avoiding false positive or false negative results by the occurrence of more than one etiologic agent. The results were analyzed through algorithmic tables, and the histologic sections were reviewed by at least three pathologists who considered morphologic changes like formation and immunologycal modulation of granulomas, the architecture, the cellular composition and the presence and extension of necrosis. It was made an evaluation of cytokines too. The results were evaluated and a medium value was adopted in the study. The HIV+ group showed poorly formed granulomas with little or none immunologycal modulation and extensive necrosis areas and a different cellular composition rich in polimorfonuclear cells. In the HIV - group the immuno-inflammatory response was completely different and it was observed typical granulomas with normal architecture, variable caseous necrosis and mainly composed by mononuclear cells. Epithelioid cells and giant cells were also found. In addition, the cytokine profiles observed were different from the literature’s data. In conclusion, there are different morphological patterns to the human pulmonary tuberculosis when comparing HIV +/ HIV - patients and these variations are closely related to the cellular immunity state of them

Lung granulomas from Mycobacterium tuberculosis/HIV-1 co-infected patients display decreased in situ TNF production.

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2014-03-13T14:01:44Z No. of bitstreams: 1 Noronha A Lung gramulomas....pdf: 1241291 bytes, checksum: 0c8fb78284e08bfc7c166f805429a8b1 (MD5)Made available in DSpace on 2014-03-13T14:01:44Z (GMT). No. of bitstreams: 1 Noronha A Lung gramulomas....pdf: 1241291 bytes, checksum: 0c8fb78284e08bfc7c166f805429a8b1 (MD5) Previous issue date: 2008Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, BrasilFederal University of Santa Catarina. Division of Immunology, Microbiology and Parasitology Departament. Florianópolis, SC, BRasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, BrasilTuberculosis/HIV-1 co-infection is responsible for thousands of deaths each year, and previous studies have reported that co-infected individuals display major morphological alterations in tissue granulomas. The purpose of this study was to evaluate immunohistopathological characteristics in lung tissues from pulmonary TB/HIV-1-co-infected individuals. Following autopsy, tuberculosis-positive HIV-1-negative cases displayed granulomas with normal architecture, mainly composed of a mononuclear infiltrate with typical epithelioid, as well as giant cells, and exhibiting caseous necrosis. In contrast, lesions from the TB/HIV-1-co-infected group showed extensive necrosis, poorly formed granulomas, and a marked presence of polymorphonuclear cells. More importantly, TNF staining was greatly reduced in the TB/HIV-1-co-infected individuals. Our data suggest that HIV-1 infection alters the organization of pulmonary granulomas by modulating TNF and, possibly, cell trafficking, leading to an impaired anti-tuberculosis response

Toward a Novel Experimental Model of Infection To Study American Cutaneous Leishmaniasis Caused by Leishmania braziliensis

Leishmania spp. cause a broad spectrum of diseases collectively known as leishmaniasis. Leishmania braziliensis is the main etiological agent of American cutaneous leishmaniasis (ACL) and mucocutaneous leishmaniasis. In the present study, we have developed an experimental model of infection that closely resembles ACL caused by L. braziliensis. In order to do so, BALB/c mice were infected in the ear dermis with 10(5) parasites and distinct aspects of the infection were evaluated. Following inoculation, parasite expansion in the ear dermis was accompanied by the development of an ulcerated dermal lesion which healed spontaneously, as seen by the presence of a scar. Histological analysis of infected ears showed the presence of a mixed inflammatory infiltrate consisting of both mononuclear and polymorphonuclear cells. In draining lymph nodes, parasite replication was detected throughout the infection. In vitro restimulation of draining lymph node cells followed by intracellular staining showed an up-regulation in the production of gamma interferon (IFN-γ) and in the frequency of IFN-γ-secreting CD4(+) and CD8(+) T cells. Reverse transcription-PCR of ears and draining lymph node cells showed the expression of CC chemokines. The dermal model of infection with L. braziliensis herein is able to reproduce aspects of the natural infection, such as the presence of an ulcerated lesion, parasite dissemination to lymphoid areas, and the development of a Th1-type immune response. These results indicate that this model shall be useful to address questions related to the concomitant immunity to reinfection and parasite persistence leading to mucocutaneous leishmaniasis

IFN-beta impairs superoxide-dependent parasite killing in human macrophages: evidence for a deleterious role of SOD1 in cutaneous leishmaniasis

Submitted by Martha Silveira Berbert ([email protected]) on 2011-04-13T00:00:14Z No. of bitstreams: 1 IFN-b Impairs Superoxide-Dependent Parasite.pdf: 1016343 bytes, checksum: 09496d8f56dbc991ddc5527a635213ad (MD5)Made available in DSpace on 2011-04-13T00:00:14Z (GMT). No. of bitstreams: 1 IFN-b Impairs Superoxide-Dependent Parasite.pdf: 1016343 bytes, checksum: 09496d8f56dbc991ddc5527a635213ad (MD5) Previous issue date: 2009-02-14Laboratório Integrado de Microbiologia e Imunoregulação. Centro de Pesquisas Gonçalo Moniz - FIOCRUZ, Bahia, BrasilLaboratório de Imunoparasitologia. Centro de Pesquisas Gonçalo Moniz - FIOCRUZ, Bahia, BrasilLaboratório Integrado de Microbiologia e Imunoregulação. Centro de Pesquisas Gonçalo Moniz - FIOCRUZ, Bahia, BrasilLaboratório Integrado de Microbiologia e Imunoregulação. Centro de Pesquisas Gonçalo Moniz - FIOCRUZ, Bahia, BrasilInstitut National de la Santé et de la Recherche Médicale (INSERM), Unité Mixte de Recherche en Santé 872, Centre de Recherche des Cordeliers, Paris, FrançaINSERM, Unité 365, Institut Curie, Paris, FrançaLaboratório de Imunoparasitologia. Centro de Pesquisas Gonçalo Moniz - FIOCRUZ, Bahia, BrasilLaboratório Integrado de Microbiologia e Imunoregulação. Centro de Pesquisas Gonçalo Moniz - FIOCRUZ, Bahia, BrasilLaboratório Integrado de Microbiologia e Imunoregulação. Centro de Pesquisas Gonçalo Moniz - FIOCRUZ, Bahia, BrasilType I IFNs (IFN-alpha/beta) have only recently gained considerable attention as immunomodulators in nonviral infectious diseases. IFN-beta has been shown to protect, in a NO-dependent manner, against murine Old World leishmaniasis caused by Leishmania major, but data in New World leishmaniasis are lacking. We found that IFN-beta dose-dependently increases parasite burden in Leishmania amazonensis- as well as Leishmania braziliensis-infected human macrophages, independent of endogenous or exogenous NO. However, IFN-beta significantly reduced superoxide release in Leishmania-infected as well as uninfected human macrophages. This decrease in superoxide production was paralleled by a significant IFN-beta-mediated increase in superoxide dismutase 1 (SOD1) protein levels. Additionally, IFN-beta inhibition of leishmanicidal activity was mimicked by SOD1 and antagonized by either pharmacological or small interfering RNA-mediated inhibition of SOD1. Finally, pronounced SOD1 expression in situ was demonstrated in biopsies from New World cutaneous leishmaniasis patients. These findings reveal a hitherto unknown IFN-beta/SOD1 axis in Leishmania infection and suggest that inhibition of SOD-associated pathways could serve as strategy in the treatment of L. amazonensis as well as L. braziliensis infection, major human pathogens

Presence of parasite DNA in clinically unaffected nasal mucosa during cutaneous leishmaniasis caused by Leishmania (Viannia) braziliensis

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2019-02-12T18:17:17Z No. of bitstreams: 1 Canário, A. Presence of parasite DNA in clinically...2019.pdf: 248161 bytes, checksum: d71cb01c750c9ac331f7e6511eef667a (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2019-02-12T18:30:42Z (GMT) No. of bitstreams: 1 Canário, A. Presence of parasite DNA in clinically...2019.pdf: 248161 bytes, checksum: d71cb01c750c9ac331f7e6511eef667a (MD5)Made available in DSpace on 2019-02-12T18:30:42Z (GMT). No. of bitstreams: 1 Canário, A. Presence of parasite DNA in clinically...2019.pdf: 248161 bytes, checksum: d71cb01c750c9ac331f7e6511eef667a (MD5) Previous issue date: 2019FAPESB e Brazil (SUS0024/ 2013). This study was financed in part by the Coordenaç~ao de Aperfeiçoamento de Pessoal de Nível Superior - Brazil (CAPES) - Finance Code 001.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Pós-Graduação em Ciências da Saúde. Salvador, BA, Brasil / Hospital Santa Izabel. Santa Casa de Misericórdia da Bahia. Serviço de Otorrinolaringologia. Salvador, BA, Brazil.Hospital Santa Izabel. Santa Casa de Misericórdia da Bahia. Serviço de Otorrinolaringologia. Salvador, BA, Brazil.Hospital Santa Izabel. Santa Casa de Misericórdia da Bahia. Serviço de Otorrinolaringologia. Salvador, BA, Brazil.Hospital Santa Izabel. Santa Casa de Misericórdia da Bahia. Serviço de Otorrinolaringologia. Salvador, BA, Brazil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Pós-Graduação em Ciências da Saúde. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Pós-Graduação em Ciências da Saúde. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Pós-Graduação em Ciências da Saúde. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Pós-Graduação em Ciências da Saúde. Salvador, BA, Brasil / Hospital Santa Izabel. Santa Casa de Misericórdia da Bahia. Serviço de Otorrinolaringologia. Salvador, BA, Brazil.We aimed to detect Leishmania DNA carriage in nasal mucosa of individuals with cutaneous leishmaniasis (CL) caused by Leishmania (Viannia) braziliensis. Methods: A cross-sectional study was performed in all individuals with CL without nasal lesions (n ¼ 153) attended within 2 years in an endemic area of L. (Viannia) braziliensis in Bahia (Brazil). An otorhinolaryngologist assessed the clinical status of the nasal mucosa by anterior rhinoscopy and endoscopic examinations. Swab samples were collected for parasite DNA detection by PCR from all individuals before standard treatment for leishmaniasis. A second evaluation 3 months after treatment was performed to assess clinical outcomes. Results: Parasite DNA was detected in 7.8% (12/153) of clinically healthy nasal mucosa of individuals with CL. Interestingly, DNA was more frequently identified in individuals with more skin lesions (median 1.5, interquartile range (IQR) 1e3.5 versus 1.0, IQR 1e1.5; p 0.044), or larger injuries (median 2.7, IQR 2e3.8 versus 1.6, IQR 1e2.5; p 0.013). Additionally, the disease of those individuals with positive PCR evolved more frequently to unusual forms of leishmaniasis (recidiva cutis and disseminated) (45.5% (5/11) versus 11.5% (14/122); p 0.009), and required more cycles of treatment to reach clinical cure (median 2, IQR 1e4 versus 1, IQR 1e2; p 0.05). Conclusion: These findings suggest an early parasite tropism to nasal mucosa in L. (Viannia) braziliensis infection and a clinical phenotype of CL cases associated with parasite DNA in nasal mucosa. Future studies should evaluate whether PCR of nasal swab samples could serve as a prognostic tool for individuals at risk of mucocutaneous leishmaniasis

CD8(+) Granzyme B(+)-Mediated Tissue Injury vs. CD4(+)IFNγ(+)-Mediated Parasite Killing in Human Cutaneous Leishmaniasis

A protective or deleterious role of CD8(+)T cells in human cutaneous leishmaniasis (CL) has been debated. The present report explores the participation of CD8(+)T cells in disease pathogenesis as well as in parasite killing. CD8(+)T cells accumulated in CL lesions as suggested by a higher frequency of CD8(+)CD45RO(+)T cells and CD8(+)CLA(+)T cells compared with peripheral blood mononuclear cells. Upon Leishmania braziliensis restimulation, most of the CD8(+)T cells from the lesion expressed cytolytic markers, CD107a and granzyme B. Granzyme B expression in CL lesions positively correlated with lesion size and percentage of TUNEL-positive cells. We also observed a significantly higher percentage of TUNEL-positive cells and granzyme B expression in the biopsies of patients showing a more intense necrotic process. Furthermore, coculture of infected macrophages and CD8(+)T lymphocytes resulted in the release of granzyme B, and the use of granzyme B inhibitor, as well as z-VAD, Fas:Fc, or anti-IFN-γ, had no effect upon parasite killing. However, coculture of infected macrophages with CD4(+)T cells strongly increased parasite killing, which was completely reversed by anti-IFN-γ. Our results reveal a dichotomy in human CL: CD8(+) granzyme B(+)T cells mediate tissue injury, whereas CD4(+)IFN-γ(+)T cells mediate parasite killing.Journal of Investigative Dermatology advance online publication, 14 February 2013; doi:10.1038/jid.2013.4.status: publishe

Integrated Analysis Reveals That miR-193b, miR-671, and TREM-1 Correlate With a Good Response to Treatment of Human Localized Cutaneous Leishmaniasis Caused by Leishmania braziliensis

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2018-05-10T16:30:18Z No. of bitstreams: 1 Nunes S Integrated Analysis Reveals That miR-193b....pdf: 4103629 bytes, checksum: 8447bfa7915208ba900d14c3effa54e5 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2018-05-10T16:49:33Z (GMT) No. of bitstreams: 1 Nunes S Integrated Analysis Reveals That miR-193b....pdf: 4103629 bytes, checksum: 8447bfa7915208ba900d14c3effa54e5 (MD5)Made available in DSpace on 2018-05-10T16:49:33Z (GMT). No. of bitstreams: 1 Nunes S Integrated Analysis Reveals That miR-193b....pdf: 4103629 bytes, checksum: 8447bfa7915208ba900d14c3effa54e5 (MD5) Previous issue date: 2018Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, BrasilLaboratório de Anatomia Patológica. Feira de Santana, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, BrasilUniversidade Federal da Bahia. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Centre for Data and Knowledge Integration for Health. Salvador, Ba, BrazilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, BrasilUniversidade Federal da Bahia. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Centre for Data and Knowledge Integration for Health. Salvador, Ba, BrazilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, BrasilLocalized cutaneous leishmaniasis (LCL) is a chronic disease characterized by ulcerated skin lesion(s) and uncontrolled inflammation. The mechanisms underlying the pathogenesis of LCL are not completely understood, and little is known about posttranscriptional regulation during LCL. MicroRNAs (miRNAs) are non-coding small RNAs that regulate gene expression and can be implicated in the pathogenesis of LCL. We investigated the involvement of miRNAs and their targets genes in human LCL using publicly available transcriptome data sets followed by ex vivo validation. Initial analysis highlighted that miRNA expression is altered during LCL, as patients clustered separately from controls. Joint analysis identified eight high confidence miRNAs that had altered expression (-1.5 ≤ fold change ≥ 1.5; p < 0.05) between cutaneous ulcers and uninfected skin. We found that the expression of miR-193b and miR-671 are greatly associated with their target genes, CD40 and TNFR, indicating the important role of these miRNAs in the expression of genes related to the inflammatory response observed in LCL. In addition, network analysis revealed that miR-193b, miR-671, and TREM1 correlate only in patients who show faster wound healing (up to 59 days) and not in patients who require longer cure times (more than 60 days). Given that these miRNAs are associated with control of inflammation and healing time, our findings reveal that they might influence the pathogenesis and prognosis of LCL

Imaging exams of bone lesions in patients with diffuse cutaneous leishmaniasis (DCL)

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2011-08-30T18:15:23Z No. of bitstreams: 1 Costa AA Imaging exams of bone....pdf: 194017 bytes, checksum: 362322b9ce5037335fdb810d85041da2 (MD5)Made available in DSpace on 2011-08-30T18:15:23Z (GMT). No. of bitstreams: 1 Costa AA Imaging exams of bone....pdf: 194017 bytes, checksum: 362322b9ce5037335fdb810d85041da2 (MD5) Previous issue date: 2004Federal University of Maranhão. Nucleus of Tropical Pathology and Social Medicine. São Luís, MA, Brasil.Federal University of Maranhão. Nucleus of Tropical Pathology and Social Medicine. São Luís, MA, Brasil.Nuclear Medicine Service. Nuclear Maranhão Clinic. São Luis, MA, Brazil.Nuclear Medicine Service. Nuclear Maranhão Clinic. São Luis, MA, Brazil.Nuclear Medicine Service. Nuclear Maranhão Clinic. São Luis, MA, Brazil.Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brazil.Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brazil.Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brazil.University of São Paulo. Laboratory of Immunopathology (LIM-50). São Paulo, SP, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brazil.We studied bone lesion alterations in three patients with diffuse cutaneous leishmaniasis (DCL) by imaging exams (radiography and scintigraphy) and histopathology. Two patients had bone lesions of distal extremities of hands and feet, and one infiltrating plaques in the skin. The study was conducted at three specialized centers (Presidente Dutra Hospital/Nucleus of Tropical Pathology, UFMA-MA; Gonc¸alo Moniz Research Center-FIOCRUZ-BA; Laboratory of Pathology of Infectious Diseases (LIM-50), University of S˜ao Paulo, SP). Three-phase bone scintigraphy demonstrated high sensitivity and specificity for bone lesions, showing increased uptake of the radiopharmaceutical at sites of active lesions. In contrast, radiography demonstrated lytic lesions, cortical destruction and local osteopenia of the bone extremeties in two patients. Histopathological analysis showed sequestration with presence of amastigote forms of Leishmania (osteomyelitis), mononuclear cells and macrophages containing amastigote forms of Leishmania in one patient. These preliminary data indicate that imaging exams (radiography and scintigraphy) are important in the evaluation of bone lesions in diffuse cutaneous leishmaniasis and should be included in the routine histopathological diagnosis of the disease and follow-up of bone lesion

CD8(+) granzyme B(+)-mediated tissue injury vs. CD4(+)IFNγ(+)-mediated parasite killing in human cutaneous leishmaniasis

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2017-08-23T19:00:23Z No. of bitstreams: 1 Silva C CD8+Granzyme B+ T cells-mediated... .pdf: 4914876 bytes, checksum: e54c8737a502be3105cd578fa7d10ef4 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2017-08-24T16:25:38Z (GMT) No. of bitstreams: 1 Silva C CD8+Granzyme B+ T cells-mediated... .pdf: 4914876 bytes, checksum: e54c8737a502be3105cd578fa7d10ef4 (MD5)Made available in DSpace on 2017-08-24T16:25:38Z (GMT). No. of bitstreams: 1 Silva C CD8+Granzyme B+ T cells-mediated... .pdf: 4914876 bytes, checksum: e54c8737a502be3105cd578fa7d10ef4 (MD5) Previous issue date: 2013Fundação de Amparo a Pesquisa do Estado da Bahia (FAPESB) e/Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq grant number PPSUS # SUS0025/2009) and from Pronex (FAPESB/CNPq grant number 738712006). CdaSS has a fellowship from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Brazil.Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilUniversidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilUniversidade de São Paulo. Faculdade de Ciências Farmacêuticas de São Paulo. Departamento de Análises Clínicas, Toxicológicas e Bromatológicas. São Paulo, SP, BrasilUniversidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilUniversidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil / Fundação 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, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Instituto de Investigação em Imunologia. São Paulo, SP, BrazilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Instituto de Investigação em Imunologia. São Paulo, SP, BrazilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Instituto de Investigação em Imunologia. São Paulo, SP, BrazilUniversidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Instituto de Investigação em Imunologia. São Paulo, SP, BrazilUniversidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Instituto de Investigação em Imunologia. São Paulo, SP, BrazilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Instituto de Investigação em Imunologia. São Paulo, SP, Brazil /A protective or deleterious role of CD8(+)T cells in human cutaneous leishmaniasis (CL) has been debated. The present report explores the participation of CD8(+)T cells in disease pathogenesis as well as in parasite killing. CD8(+)T cells accumulated in CL lesions as suggested by a higher frequency of CD8(+)CD45RO(+)T cells and CD8(+)CLA(+)T cells compared with peripheral blood mononuclear cells. Upon Leishmania braziliensis restimulation, most of the CD8(+)T cells from the lesion expressed cytolytic markers, CD107a and granzyme B. Granzyme B expression in CL lesions positively correlated with lesion size and percentage of TUNEL-positive cells. We also observed a significantly higher percentage of TUNEL-positive cells and granzyme B expression in the biopsies of patients showing a more intense necrotic process. Furthermore, coculture of infected macrophages and CD8(+)T lymphocytes resulted in the release of granzyme B, and the use of granzyme B inhibitor, as well as z-VAD, Fas:Fc, or anti-IFN-γ, had no effect upon parasite killing. However, coculture of infected macrophages with CD4(+)T cells strongly increased parasite killing, which was completely reversed by anti-IFN-γ. Our results reveal a dichotomy in human CL: CD8(+) granzyme B(+)T cells mediate tissue injury, whereas CD4(+)IFN-γ(+)T cells mediate parasite killing