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

Aspectos inerentes à saúde mental do enfermeiro no combate a Pandemia da COVID-19

O presente estudo tem a finalidade de identificar as situações que comprometem a saúde mental e física dos profissionais de enfermagem, durante a pandemia; bem como demonstrar as razões que contribuem com o desenvolvimento de enfermidades físicas e mentais durante a pandemia. Metodologia: trata-se de uma revisão sistemática da literatura. foram utilizadas as seguintes bases de dados: Scientific Eletronic Library Online (SciELO), Biblioteca Virtual em Saúde (BVS), e Google Scholar, por meio de descritores: Saúde Mental; Pandemia; Covid-19; Ansiedade; Depressão; Enfermagem e Saúde. Após realizar o cruzamento dos descritores e incluindo os critérios de inclusão, finalizou-se com a seleção de 11 artigos relacionados a esse tema Resultados: Nas literaturas analisadas evidenciou-se uma alta taxa de adoecimento mental e físico e infelizmente número de morbimortalidades entre enfermeiros, técnicos e auxiliares de enfermagem, incluídos temas relacionados a depressão, ansiedade, medo, número de casos de contaminação dentro do contexto enfermagem, insalubridade, sobrecarga de trabalho

Differential regulation of lung homeostasis and silicosis by the TAM receptors MerTk and Axl

IntroductionTAM receptor-mediated efferocytosis plays an important function in immune regulation and may contribute to antigen tolerance in the lungs, a site with continuous cellular turnover and generation of apoptotic cells. Some studies have identified failures in efferocytosis as a common driver of inflammation and tissue destruction in lung diseases. Our study is the first to characterize the in vivo function of the TAM receptors, Axl and MerTk, in the innate immune cell compartment, cytokine and chemokine production, as well as the alveolar macrophage (AM) phenotype in different settings in the airways and lung parenchyma.MethodsWe employed MerTk and Axl defective mice to induce acute silicosis by a single exposure to crystalline silica particles (20 mg/50 μL). Although both mRNA levels of Axl and MerTk receptors were constitutively expressed by lung cells and isolated AMs, we found that MerTk was critical for maintaining lung homeostasis, whereas Axl played a role in the regulation of silica-induced inflammation. Our findings imply that MerTk and Axl differently modulated inflammatory tone via AM and neutrophil recruitment, phenotype and function by flow cytometry, and TGF-β and CXCL1 protein levels, respectively. Finally, Axl expression was upregulated in both MerTk-/- and WT AMs, confirming its importance during inflammation.ConclusionThis study provides strong evidence that MerTk and Axl are specialized to orchestrate apoptotic cell clearance across different circumstances and may have important implications for the understanding of pulmonary inflammatory disorders as well as for the development of new approaches to therapy

Estimulação cerebral profunda na Doença de Parkinson: evidências de estudos de longa duração

A Doença de Parkinson (DP) é uma condição neurodegenerativa crônica que afeta principalmente idosos, mas pode ocorrer em adultos jovens. É a segunda doença neurodegenerativa mais comum, após o Alzheimer. A DP afeta 1% dos indivíduos acima de 60 anos em países industrializados. Sua causa envolve fatores genéticos e ambientais, como exposição a pesticidas e envelhecimento. A Estimulação Cerebral Profunda (DBS) é um tratamento que simula lesões cerebrais, melhorando sintomas motores e não motores. O presente estudo tem como objetivo analisar evidências de estudos sobre a eficácia da DBS no tratamento da DP. Trata-se de uma revisão sistemática de estudos quantitativos que utiliza as bases de dados PubMed (Medline), Cochrane Library e Scientific Electronic Library Online (SciELO) para selecionar artigos científicos. Os estudos incluídos abrangem o período de 2013 a 2023 e estão em inglês, abordando a DBS no tratamento da DP. A DBS melhora diversos sintomas motores e não motores, resultando em uma melhor qualidade de vida para os pacientes. Tais benefícios são sustentados mesmo em estágios avançados da Doença de Parkinson, a qual consiste em fornecer pulsos de corrente elétrica a áreas cerebrais profundas através de eletrodos implantados cirurgicamente, geralmente quando a terapia medicamentosa já não é eficaz. Em um estudo com 82 pacientes, a terapia com DBS resultou em uma redução de ± 52% nos sintomas motores do UPDRS sob medicação antes da cirurgia. A melhora nos sintomas motores com a estimulação, em comparação com a ausência de estimulação e medicação, foi de ± 61% no primeiro ano e ± 39% de 8 a 15 anos após a cirurgia (antes da reprogramação). A medicação foi reduzida em ± 55% após 1 ano e ± 44% após 8 a 15 anos, com a maioria dos pacientes mostrando melhorias após a reprogramação. De acordo com as literaturas analisadas, a DBS é uma terapia eficaz para a DP. Enfatiza-se a importância da inovação contínua e dos novos estudos para explorar as facetas não investigadas desse campo. Com a abordagem dos aspectos clínicos, cirúrgicos, tecnológicos e científicos, destacam-se os benefícios, limitações e desafios a serem superados. Ademais, inovações tecnológicas na DBS, como a estimulação direcional, adaptativa e a telemedicina estão sendo exploradas. Em suma, este artigo fornece evidências sobre os benefícios da DBS na DP, ressaltando a necessidade de pesquisas adicionais para otimizar tal intervenção terapêutica e melhorar a qualidade de vida dos pacientes

Cellular Stress and Senescence Induction during Trypanosoma cruzi Infection

Chagas disease (CD) is a neglected tropical disease caused by Trypanosoma cruzi infection that, despite being discovered over a century ago, remains a public health problem, mainly in developing countries. Since T. cruzi can infect a wide range of mammalian host cells, parasite–host interactions may be critical to infection outcome. The intense immune stimulation that helps the control of the parasite’s replication and dissemination may also be linked with the pathogenesis and symptomatology worsening. Here, we discuss the findings that support the notion that excessive immune system stimulation driven by parasite persistence might elicit a progressive loss and collapse of immune functions. In this context, cellular stress and inflammatory responses elicited by T. cruzi induce fibroblast and other immune cell senescence phenotypes that may compromise the host’s capacity to control the magnitude of T. cruzi-induced inflammation, contributing to parasite persistence and CD progression. A better understanding of the steps involved in the induction of this chronic inflammatory status, which disables host defense capacity, providing an extra advantage to the parasite and predisposing infected hosts prematurely to immunosenescence, may provide insights to designing and developing novel therapeutic approaches to prevent and treat Chagas disease

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

Ecology of Lutzomyia longipalpis in an area of visceral leishmaniasis transmission in north-eastern Brazil

Submitted by Kamylla Nascimento ([email protected]) on 2017-12-15T13:44:30Z No. of bitstreams: 1 art. Ecology of Lutzomyia - costa.pdf: 357884 bytes, checksum: 32d6c5f26e4f67d61524ffacffc60027 (MD5)Approved for entry into archive by Kamylla Nascimento ([email protected]) on 2017-12-15T13:58:04Z (GMT) No. of bitstreams: 1 art. Ecology of Lutzomyia - costa.pdf: 357884 bytes, checksum: 32d6c5f26e4f67d61524ffacffc60027 (MD5)Made available in DSpace on 2017-12-15T13:58:05Z (GMT). No. of bitstreams: 1 art. Ecology of Lutzomyia - costa.pdf: 357884 bytes, checksum: 32d6c5f26e4f67d61524ffacffc60027 (MD5) Previous issue date: 2013Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Departamento de imunologia. Recife, PE, Brasil.Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Departamento de imunologia. Recife, PE, Brasil / Università degli Studi di Bari. Dipartimento di Medicina Veterinaria. Valenzano, Bari, Italy.Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Departamento de imunologia. Recife, PE, Brasil.Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Departamento de imunologia. Recife, PE, Brasil.Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Departamento de imunologia. Recife, PE, Brasil.Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Departamento de imunologia. Recife, PE, Brasil.Visceral leishmaniasis is a major public health issue in South America, where the disease is rapidly spreading. Changes in ecology and distribution of the principal vector, Lutzomyia longipalpis are among the factors accounting for the increasing incidence of the disease in this region. However, information about the ecology of L. longipalpis is still incipient, which may directly impair the implementation of effective control programs. Herein, the ecology of L. longipalpis was studied in a focus of visceral leishmaniasis in north-eastern Brazil. From August 2009 to August 2010, phlebotomine sand flies were monthly collected in four localities using CDC light traps (~37 per month) and a lantern-baited Shannon trap with mouth aspirators. A total of 24,226 phlebotomine sand flies were collected with light traps and 375 with mouth aspirators. The most abundant species was L. longipalpis, representing 97.9% of the specimens collected with light traps and 91.5% with the mouth aspirator. Other species (Lutzomyia evandroi, Lutzomyia lenti and Lutzomyia sallesi) were found in low numbers. Most phlebotomine sand flies (94.6%) were collected at chicken coops and corrals. No significant correlation was found between the monthly abundance of phlebotomine sand flies and the monthly averages of temperature, relative humidity or rainfall. However, interestingly enough, 82.4% of L. longipalpis specimens were collected in months when relative humidity surpassed 75%. This study points out that this vector is well adapted to live in different habitats and to different climate conditions. It also suggests that some north-eastern populations of L. longipalpis may be more xerotolerant than southern populations. Further studies to assess the relationship between microclimate and L. longipalpis density in different Brazilian regions are advised

Ecology of Lutzomyia longipalpis in an area of visceral leishmaniasis transmission in north-eastern Brazil

Submitted by Kamylla Nascimento ([email protected]) on 2017-12-15T13:44:30Z No. of bitstreams: 1 art. Ecology of Lutzomyia - costa.pdf: 357884 bytes, checksum: 32d6c5f26e4f67d61524ffacffc60027 (MD5)Approved for entry into archive by Kamylla Nascimento ([email protected]) on 2017-12-15T13:58:04Z (GMT) No. of bitstreams: 1 art. Ecology of Lutzomyia - costa.pdf: 357884 bytes, checksum: 32d6c5f26e4f67d61524ffacffc60027 (MD5)Made available in DSpace on 2017-12-15T13:58:05Z (GMT). No. of bitstreams: 1 art. Ecology of Lutzomyia - costa.pdf: 357884 bytes, checksum: 32d6c5f26e4f67d61524ffacffc60027 (MD5) Previous issue date: 2013Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Departamento de imunologia. Recife, PE, Brasil.Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Departamento de imunologia. Recife, PE, Brasil / Università degli Studi di Bari. Dipartimento di Medicina Veterinaria. Valenzano, Bari, Italy.Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Departamento de imunologia. Recife, PE, Brasil.Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Departamento de imunologia. Recife, PE, Brasil.Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Departamento de imunologia. Recife, PE, Brasil.Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Departamento de imunologia. Recife, PE, Brasil.Visceral leishmaniasis is a major public health issue in South America, where the disease is rapidly spreading. Changes in ecology and distribution of the principal vector, Lutzomyia longipalpis are among the factors accounting for the increasing incidence of the disease in this region. However, information about the ecology of L. longipalpis is still incipient, which may directly impair the implementation of effective control programs. Herein, the ecology of L. longipalpis was studied in a focus of visceral leishmaniasis in north-eastern Brazil. From August 2009 to August 2010, phlebotomine sand flies were monthly collected in four localities using CDC light traps (~37 per month) and a lantern-baited Shannon trap with mouth aspirators. A total of 24,226 phlebotomine sand flies were collected with light traps and 375 with mouth aspirators. The most abundant species was L. longipalpis, representing 97.9% of the specimens collected with light traps and 91.5% with the mouth aspirator. Other species (Lutzomyia evandroi, Lutzomyia lenti and Lutzomyia sallesi) were found in low numbers. Most phlebotomine sand flies (94.6%) were collected at chicken coops and corrals. No significant correlation was found between the monthly abundance of phlebotomine sand flies and the monthly averages of temperature, relative humidity or rainfall. However, interestingly enough, 82.4% of L. longipalpis specimens were collected in months when relative humidity surpassed 75%. This study points out that this vector is well adapted to live in different habitats and to different climate conditions. It also suggests that some north-eastern populations of L. longipalpis may be more xerotolerant than southern populations. Further studies to assess the relationship between microclimate and L. longipalpis density in different Brazilian regions are advised

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

Submitted by Sandra Infurna ([email protected]) on 2019-02-05T14:21:19Z No. of bitstreams: 1 alexandre2_morrot_etal_IOC_2018.pdf: 2547165 bytes, checksum: 3c339420d50f9918dcac548b2244b769 (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2019-02-05T14:36:28Z (GMT) No. of bitstreams: 1 alexandre2_morrot_etal_IOC_2018.pdf: 2547165 bytes, checksum: 3c339420d50f9918dcac548b2244b769 (MD5)Made available in DSpace on 2019-02-05T14:36:28Z (GMT). No. of bitstreams: 1 alexandre2_morrot_etal_IOC_2018.pdf: 2547165 bytes, checksum: 3c339420d50f9918dcac548b2244b769 (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 Microbiologia Paulo de Góes. Departamento de Imunologia. 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 Microbiologia Paulo de Góes. Departamento de Imunologia. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Faculdade de Medicina. 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 / Instituto Nacional para Pesquisa Translacional em Saúde e Ambiente na Região Amazônica. Conselho Nacional de Desenvolvimento Científico e Tecnológico. 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. Departamento de Imunologia. Rio de Janeiro, RJ, Brasil.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

Axl receptor induces efferocytosis, dampens M1 macrophage responses and promotes heart pathology in Trypanosoma cruzi infection

The tyrosine kinase receptor Axl induces efferocytosis, disrupts M1 responses, and promotes parasite infection and heart pathology in experimental Chagas disease