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ARCA - Access to Research and Communication Annals - IGC Repository (621 recursos)

The Institutional Repository of Instituto Gulbenkian de Ciência, developed under the project RCAAP, is intended to collect, preserve and promote open access to the intellectual production of their researchers.

DG - Artigos em revistas científicas

Mostrando recursos 1 - 16 de 16

  1. HGF Secreted by Activated Kupffer Cells Induces Apoptosis of Plasmodium-Infected Hepatocytes

    Gonçalves, Lígia Antunes; Rodo, Joana; Rodrigues-Duarte, Lurdes; de Moraes, Luciana Vieira; Penha-Gonçalves, Carlos
    Malaria liver stage infection is an obligatory parasite development step and represents a population bottleneck in Plasmodium infections, providing an advantageous target for blocking parasite cycle progression. Parasite development inside hepatocytes implies a gross cellular insult evoking innate host responses to counteract intra-hepatocytic infection. Using primary hepatocyte cultures, we investigated the role of Kupffer cell-derived hepatocyte growth factor (HGF) in malaria liver stage infection. We found that Kupffer cells from Plasmodium-infected livers produced high levels of HGF, which trigger apoptosis of infected hepatocytes through a mitochondrial-independent apoptosis pathway. HGF action in infected hepatocyte primary cultures results in a potent reduction...

  2. A New Mouse Model That Spontaneously Develops Chronic Liver Inflammation and Fibrosis

    Fransén-Pettersson, Nina; Duarte, Nadia; Nilsson, Julia; Lundholm, Marie; Mayans, Sofia; Larefalk, Åsa; Hannibal, Tine D; Hansen, Lisbeth; Schmidt-Christensen, Anja; Ivars, Fredrik; Cardell, Susanna; Palmqvist, Richard; Rozell, Björn; Holmberg, Dan
    Here we characterize a new animal model that spontaneously develops chronic inflammation and fibrosis in multiple organs, the non-obese diabetic inflammation and fibrosis (N-IF) mouse. In the liver, the N-IF mouse displays inflammation and fibrosis particularly evident around portal tracts and central veins and accompanied with evidence of abnormal intrahepatic bile ducts. The extensive cellular infiltration consists mainly of macrophages, granulocytes, particularly eosinophils, and mast cells. This inflammatory syndrome is mediated by a transgenic population of natural killer T cells (NKT) induced in an immunodeficient NOD genetic background. The disease is transferrable to immunodeficient recipients, while polyclonal T cells from...

  3. Diabetes hinders community-acquired pneumonia outcomes in hospitalized patients

    Martins, M; Boavida, J M; Raposo, J F; Froes, F; Nunes, B; Ribeiro, R T; Macedo, M P; Penha-Gonçalves, C
    This study aimed to estimate the prevalence of diabetes mellitus (DM) in hospitalized patients with community-acquired pneumonia (CAP) and its impact on hospital length of stay and in-hospital mortality.

  4. Murine Model for Preclinical Studies of Var2CSA-Mediated Pathology Associated with Malaria in Pregnancy

    de Moraes, Luciana V.; Dechavanne, Sebastien; Sousa, Patrícia M.; Barateiro, André; Cunha, Sónia F.; Nunes-Silva, Sofia; Lima, Flávia A.; Murillo, Oscar; Marinho, Claudio R. F.; Gangnard, Stephane; Srivastava, Anand; Braks, Joanna A.; Janse, Chris J.; Gamain, Benoit; Franke-Fayard, Blandine; Penha-Gonçalves, Carlos
    Plasmodium falciparum infection during pregnancy leads to abortions, stillbirth, low birth weight, and maternal mortality. Infected erythrocytes (IEs) accumulate in the placenta by adhering to chondroitin sulfate A (CSA) via var2CSA protein exposed on the P. falciparum IE membrane. Plasmodium berghei IE infection in pregnant BALB/c mice is a model for severe placental malaria (PM). Here, we describe a transgenic P. berghei parasite expressing the full-length var2CSA extracellular region (domains DBL1X to DBL6ε) fused to a P. berghei exported protein (EMAP1) and characterize a var2CSA-based mouse model of PM. BALB/c mice were infected at midgestation with different doses of P....

  5. Placental Malaria: From Infection to Malfunction

    de Moraes, Luciana Vieira; Penha-Gonçalves, Carlos
    Malaria during pregnancy is a major factor in infant morbidity and mortality. In this issue of Cell Host and Microbe, Conroy et al. (2013) propose that C5a, a product of complement cascade activation, counteracts the placental vascular remodeling response induced by Plasmodium infection and contributes to fetal growth restriction.

  6. SNP typing reveals similarity in Mycobacterium tuberculosis genetic diversity between Portugal and Northeast Brazil

    Lopes, Joao S.; Marques, Isabel; Soares, Patricia; Nebenzahl-Guimaraes, Hanna; Costa, Joao; Miranda, Anabela; Duarte, Raquel; Alves, Adriana; Macedo, Rita; Duarte, Tonya A.; Barbosa, Theolis; Oliveira, Martha; Nery, Joilda S.; Boechat, Neio; Pereira, Susan M.; Barreto, Mauricio L.; Pereira-Leal, Jose; Gomes, Maria Gabriela Miranda; Penha-Goncalves, Carlos
    Human tuberculosis is an infectious disease caused by bacteria from the Mycobacterium tuberculosis complex (MTBC). Although spoligotyping and MIRU-VNTR are standard methodologies in MTBC genetic epidemiology, recent studies suggest that Single Nucleotide Polymorphisms (SNP) are advantageous in phylogenetics and strain group/lineages identification. In this work we use a set of 79 SNPs to characterize 1987 MTBC isolates from Portugal and 141 from Northeast Brazil. All Brazilian samples were further characterized using spolygotyping. Phylogenetic analysis against a reference set revealed that about 95% of the isolates in both populations are singly attributed to bacterial lineage 4. Within this lineage, the most...

  7. IFNAR1 Controls Progression to Cerebral Malaria in Children and CD8+ T Cell Brain Pathology in Plasmodium berghei-Infected Mice

    Ball, E. A.; Sambo, M. R.; Martins, M.; Trovoada, M. J.; Benchimol, C.; Costa, J.; Antunes Goncalves, L.; Coutinho, A.; Penha-Goncalves, C.
    Development of cerebral malaria (CM), a severe and fatal form of clinical Plasmodium falciparum infection, results from a damaging cascade of vascular, inflammatory, and immunological host responses that leads to brain injury. Progression to CM can be modified by host genetic factors. Our case-control study in Angolan children aimed at highlighting the role of IFN (α, β) receptor 1 (IFNAR1) in progression to CM. We report a robust association between IFNAR1 and CM protection, as well as detailed studies showing analogous protection from experimental CM in Ifnar1(-/-) mice infected with P. berghei ANKA. We developed a novel cell-transfer protocol that...

  8. How Inflammation Impinges on NAFLD: A Role for Kupffer Cells

    Duarte, Nádia; Coelho, Inês C.; Patarrão, Rita S.; Almeida, Joana I.; Penha-Gonçalves, Carlos; Macedo, M. Paula
    Nonalcoholic fatty liver disease (NAFLD) is rapidly becoming the most prevalent cause of liver disease worldwide and afflicts adults and children as currently associated with obesity and insulin resistance. Even though lately some advances have been made to elucidate the mechanism and causes of the disease much remains unknown about NAFLD. The aim of this paper is to discuss the present knowledge regarding the pathogenesis of the disease aiming at the initial steps of NAFLD development, when inflammation impinges on fat liver deposition. At this stage, the Kupffer cells attain a prominent role. This knowledge becomes subsequently relevant for the...

  9. The Liver Plays a Major Role in Clearance and Destruction of Blood Trypomastigotes in Trypanosoma cruzi Chronically Infected Mice

    Sardinha, L. R.; Mosca, T.; Elias, R. M.; do Nascimento, R. S.; Goncalves, L. A.; Bucci, D. Z.; Marinho, C. R. F.; Penha-Goncalves, C.; Lima, M. R. D.; Alvarez, J. M.
    Intravenous challenge with Trypanosoma cruzi can be used to investigate the process and consequences of blood parasite clearance in experimental Chagas disease. One hour after intravenous challenge of chronically infected mice with 5x10(6) trypomastigotes, the liver constituted a major site of parasite accumulation, as revealed by PCR. Intact parasites and/or parasite remnants were visualized at this time point scattered in the liver parenchyma. Moreover, at this time, many of liver-cleared parasites were viable, as estimated by the frequency of positive cultures, which considerably diminished after 48 h. Following clearance, the number of infiltrating cells in the hepatic tissue notably increased:...

  10. Transforming Growth Factor Beta 2 and Heme Oxygenase 1 Genes Are Risk Factors for the Cerebral Malaria Syndrome in Angolan Children

    Sambo, Maria Rosário; Trovoada, Maria Jesus; Benchimol, Carla; Quinhentos, Vatúsia; Gonçalves, Lígia; Velosa, Rute; Marques, Maria Isabel; Sepúlveda, Nuno; Clark, Taane G.; Mustafa, Stefan; Wagner, Oswald; Coutinho, António; Penha-Gonçalves, Carlos; Rodrigues, Mauricio Martins
    BACKGROUND: Cerebral malaria (CM) represents a severe outcome of the Plasmodium falciparum infection. Recent genetic studies have correlated human genes with severe malaria susceptibility, but there is little data on genetic variants that increase the risk of developing specific malaria clinical complications. Nevertheless, susceptibility to experimental CM in the mouse has been linked to host genes including Transforming Growth Factor Beta 2 (TGFB2) and Heme oxygenase-1 (HMOX1). Here, we tested whether those genes were governing the risk of progressing to CM in patients with severe malaria syndromes. METHODOLOGY/PRINCIPAL FINDINGS: We report that the clinical outcome of P. falciparum infection in a cohort of...

  11. Non-HLA autoimmunity genetic factors contributing to Autoimmune Polyglandular Syndrome type II in Tunisian patients

    Fourati, Hajer; Bouzid, Dorra; Abida, Olfa; Kharrat, Najla; Mnif, Fatma; Haddouk, Samy; Fesel, Constantin; Costa, João; Ayed, Mourad Ben; Abid, Mohamed; Rebai, Ahmed; Penha-Gonçalves, Carlos; Masmoudi, Hatem
    Autoimmune Polyglandular Syndrome Type II (APSII) is characterized by the co-occurrence of clinical insufficiency of at least two endocrine glands. Although, HLA determinants of APSII predisposition have been identified, little attention has been paid to non-HLA genes. Here, we used SNP genotyping in a Sequenom platform and genetic association tests to study a cohort of 60 APSII Tunisian patients presenting highly frequent co-occurrence of Autoimmune Thyroid Disease (AITD) and Type 1 Diabetes (T1D) and lower frequency of Addison's disease (AD). We tested the high a priori possibility that well-established non-HLA autoimmunity loci were involved in APSII and confirmed five association...

  12. Regulatory T cells Contribute to Diabetes Protection in Lipopolysaccharide-Treated Non-Obese Diabetic Mice

    Caramalho, I; Rodrigues-Duarte, L; Perez, A; Zelenay, S; Penha-Gonçalves, C; Demengeot, J.
    It is well established that viral, parasitic or bacterial infections can prevent type 1 diabetes (T1D) occurrence in non-obese diabetic (NOD) mice. On the other hand, defects in CD4(+) Regulatory T cell (Treg) numbers and/or function contribute to T1D aetiology in NOD mice and in humans. In this work, we formally tested whether the protective role of the bacterial product lipopolysaccharide (LPS) on diabetes incidence results from enhanced Treg activity. We first report that weekly administration of LPS to young prediabetic NOD mice, presenting or not insulitis at the time of treatment, afforded full protection from diabetes. Taking advantage from...

  13. Association of the RAVER2 gene with increased susceptibility for ulcerative colitis

    Bouzid, D.; Fourati, H.; Amouri, A.; Marques, I.; Abida, O.; Haddouk, S.; Ben Ayed, M.; Tahri, N.; Penha-Gonçalves, C; Masmoudi, H.
    Crohn's disease (CD), ulcerative colitis (UC), systemic lupus erythematosus (SLE) and autoimmune polyglandular syndromes (APS) are autoimmune diseases (ADs) that may share common susceptibility pathways. We examined ribonucleo-protein, polypyrimidine tract-binding protein (PTB)-binding 2 (RAVER2) loci for these diseases in a cohort of 39 CD cases, 67 UC cases, 93 SLE cases, 60 APS cases and 162 healthy control subjects of Tunisian origin. We genotyped 3 SNPs of RAVER2 (rs2780814, rs1333739 and rs2780889) and evaluated it genetic association with each ADs, using X2-test. For each association, odds ratio (OR) and 95% CI were calculated. We show that rs2780814 is significantly associated...

  14. The {CREM} gene is involved in genetic predisposition to inflammatory bowel disease in the Tunisian population

    Bouzid, Dorra; Fourati, Hajer; Amouri, Ali; Marques, Isabel; Abida, Olfa; Haddouk, Samy; Ben Ayed, Mourad; Tahri, Nabil; Penha-Gonçalves, Carlos; Masmoudi, Hatem
    The identification of susceptibility genes for inflammatory bowel disease (IBD) is key to understanding pathogenic mechanisms. Recently, the results of genetic association studies have highlighted many loci that are shared among several autoimmune diseases. We aimed to study the genetic epidemiology of polymorphisms in specific genes previously associated with other autoimmune diseases, namely the CREM, STAT4, STAT5a, Stat5b, and IRF5 genes. Twelve polymorphisms in the CREM, STAT4, STAT5a, Stat5b, and IRF5 genes were genotyped in a cohort of 107 IBD patients (39 Crohn's disease [CD] and 68 ulcerative colitis [UC]) and 162 controls from southern Tunisia. One CREM single nucleotide...

  15. IFNAR1 Controls Progression to Cerebral Malaria in Children and CD8+ T Cell Brain Pathology in Plasmodium berghei-Infected Mice

    Ball, E. A.; Sambo, M. R.; Martins, M.; Trovoada, M. J.; Benchimol, C.; Costa, J.; Antunes Goncalves, L.; Coutinho, A.; Penha-Goncalves, C.
    Malaria in pregnancy is exquisitely aggressive, causing a range of adverse maternal and fetal outcomes prominently linked to Plasmodium-infected erythrocyte cytoadherence to fetal trophoblast. To elucidate the physiopathology of infected erythrocytes (IE) sequestration in the placenta we devised an experimental system for intravital placental examination of P. berghei-infected mice. BALB/c females were mated to C57Bl/6 CFP+ male mice and infected with GFP+ P. berghei IE, and at gestational day 18, placentas were exposed for time-lapse imaging acquisition under two-photon microscopy. Real-time images and quantitative measurements revealed that trophoblast conformational changes transiently restrain blood flow in the mouse placental labyrinth. The...

  16. Intravital placenta imaging reveals microcirculatory dynamics impact on sequestration and phagocytosis of Plasmodium-infected erythrocytes

    Moraes, Luciana Vieira de; Tadokoro, Carlos Eduardo; Gómez-Conde, Ivan; Olivieri, David N.; Penha-Gonçalves, Carlos
    Malaria in pregnancy is exquisitely aggressive, causing a range of adverse maternal and fetal outcomes prominently linked to Plasmodium-infected erythrocyte cytoadherence to fetal trophoblast. To elucidate the physiopathology of infected erythrocytes (IE) sequestration in the placenta we devised an experimental system for intravital placental examination of P. berghei-infected mice. BALB/c females were mated to C57Bl/6 CFP+ male mice and infected with GFP+ P. berghei IE, and at gestational day 18, placentas were exposed for time-lapse imaging acquisition under two-photon microscopy. Real-time images and quantitative measurements revealed that trophoblast conformational changes transiently restrain blood flow in the mouse placental labyrinth. The...

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