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

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

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

Cellular Stress and Senescence Induction during <i>Trypanosoma cruzi</i> 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

Flebotomíneos (Diptera: Psychodidae) em São Vicente Férrer, uma área simpátrica para leishmaniose tegumentar e visceral, no estado de Pernambuco, Brasil

Submitted by Kamylla Nascimento ([email protected]) on 2018-04-16T12:49:38Z No. of bitstreams: 1 Phlebotomine sandflies (Diptera Psychodidae) in São Vicente Férrer.pdf: 901490 bytes, checksum: c081ede1d1081e982ac5bb4cc1bad2bd (MD5)Approved for entry into archive by Kamylla Nascimento ([email protected]) on 2018-04-16T12:55:49Z (GMT) No. of bitstreams: 1 Phlebotomine sandflies (Diptera Psychodidae) in São Vicente Férrer.pdf: 901490 bytes, checksum: c081ede1d1081e982ac5bb4cc1bad2bd (MD5)Made available in DSpace on 2018-04-16T12:55:49Z (GMT). No. of bitstreams: 1 Phlebotomine sandflies (Diptera Psychodidae) in São Vicente Férrer.pdf: 901490 bytes, checksum: c081ede1d1081e982ac5bb4cc1bad2bd (MD5) Previous issue date: 2012Esta pesquisa foi apoiada pela Fundação de Amparo à Ciência e Tecnologia do Estado de Pernambuco (FACEPE), APQ-0630-2.13 / 08.Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil.Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil.Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil.Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil.Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil.Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil.Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil.Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil.INTRODUÇÃO: Nas últimas décadas tem se observado uma considerável expansão geográfica das leishmanioses em todas as regiões do Brasil. O presente estudo foi realizado para identificar a fauna de flebotomíneos e verificar a sazonalidade das principais espécies após mudanças ambientais ocorridas no município de São Vicente Férrer, Estado de Pernambuco, Brasil. MÉTODOS: As capturas foram realizadas durante quatro noites consecutivas por mês usando armadilhas luminosas CDC, no período de setembro de 2009 a setembro de 2010. A correlação entre o número de flebotomíneos capturados e fatores climáticos (temperatura e umidade) foi avaliada. RESULTADOS: Foi capturado um total de 13.872 espécimes pertencentes a 20 espécies, sendo 6.247 (45%) fêmeas e 7.625 (55%) machos. Lutzomyia migonei foi a espécie mais abundante com 9.964 (71,8%) espécimes, sendo predominante no intradomicílio 108 (86,4%) e peridomicílio 9.746 (97%). Nos resquícios de mata primária, predominaram Lutzomyia complexa 2.395 (65%) e Lutzomyia sordellii 770 (20,8%). A análise de correlação entre o número total de flebotomíneos capturados e os fatores climáticos não mostrou uma influência significativa na densidade da população. CONCLUSÕES: A elevada abundância de Lutzomyia migonei e Lutzomyia complexa indica a possibilidade de novos casos de leishmaniose cutânea (LC).INTRODUCTION: In the last decades, a considerable geographic expansion of the leishmaniases in all regions of Brazil has been observed. The present study was carried out to identify the composition of the phlebotomine sandfly fauna and verify the seasonal variation of the main species after environmental changes occurred in São Vicente Férrer Municipality, State of Pernambuco, Brazil. METHODS: Captures were carried out during four consecutive nights of each month using Centers for Disease Control and Prevention light traps from September 2009 to September 2010. The correlation between the number of phlebotomine sandflies captured and climatic factors (temperature and rainfall) was evaluated. RESULTS: A total of 13,872 specimens belonging to 20 species were captured, of which, 6,247 (45%) were females, and 7,625 (55%) were males. Lutzomyia migonei was the most abundant species with 9,964 (71.8%) specimens, being predominant in the intradomicile and peridomicile areas with 108 (86.4%) and 9,746 (97%), respectively. In the forest remnants, Lutzomyia complexa 2,395 (65%) and Lutzomyia sordellii 770 (20.8%) predominated. The correlation analysis between the total number of sandflies captured and climatic factors did not show a significant influence on population density. CONCLUSIONS: The high abundance of Lutzomyia migonei and Lutzomyia complexa indicates the possibility of new cases of cutaneous leishmaniasis (CL)

Immune Responses in Leishmaniasis: An Overview

Leishmaniasis is a parasitic, widespread, and neglected disease that affects more than 90 countries in the world. More than 20 Leishmania species cause different forms of leishmaniasis that range in severity from cutaneous lesions to systemic infection. The diversity of leishmaniasis forms is due to the species of parasite, vector, environmental and social factors, genetic background, nutritional status, as well as immunocompetence of the host. Here, we discuss the role of the immune system, its molecules, and responses in the establishment, development, and outcome of Leishmaniasis, focusing on innate immune cells and Leishmania major interactions