Investigaçao de lectina ligante de manose (MBL) em pacientes com doença celíaca

Orientadora : Iara Taborda de Messias ReasonCo-orientadora: Shirley Ramos da Rosa UtiyamaInclui apendiceDissertaçao (mestrado) - Universidade Federal do Paraná, Setor de Ciencias da Saúde, Programa de Pós-Graduaçao em Ciencias Farmaceuticas. Defesa: Curitiba, 2006Inclui bibliografia e anexoÁrea de concentraçao: Análises clínica

Parasite-host interaction in malaria: genetic clues and copy number variation

In humans, infections contribute highly to mortality and morbidity rates worldwide. Malaria tropica is one of the major infectious diseases globally and is caused by the protozoan parasite Plasmodium falciparum. Plasmodia have accompanied human beings since the emergence of humankind. Due to its pathogenicity, malaria is a powerful selective force on the human genome. Genetic epidemiology approaches such as family and twin studies, candidate gene studies, and disease-association studies have identified a number of genes that mediate relative protection against the severest forms of the disease. New molecular approaches, including genome-wide association studies, have recently been performed to expand our knowledge on the functional effect of human variation in malaria. For the future, a systematic determination of gene-dosage effects and expression profiles of protective genes might unveil the functional impact of structural alterations in these genes on either side of the host-parasite interaction

Limited response of NK92 cells to Plasmodium falciparum-infected erythrocytes

<p>Abstract</p> <p>Background</p> <p>Mechanisms by which anti-malarial immune responses occur are still not fully clear. Natural killer (NK) cells are thought to play a pivotal role in innate responses against <it>Plasmodium falciparum</it>. In this study, the suitability of NK92 cells as models for the NK mechanisms involved in the immune response against malaria was investigated.</p> <p>Methods</p> <p>NK92 cells were assessed for several signs of activation and cytotoxicity due to contact to parasites and were as well examined by oligonucleotide microarrays for an insight on the impact <it>P. falciparum</it>-infected erythrocytes have on their transcriptome. To address the parasite side of such interaction, growth inhibition assays were performed including non-NK cells as controls.</p> <p>Results</p> <p>By performing microarrays with NK92 cells, the impact of parasites on a transcriptional level was observed. The findings show that, although not evidently activated by iRBCs, NK92 cells show transcriptional signs of priming and proliferation. In addition, decreased parasitaemia was observed due to co-incubation with NK92 cells. However, such effect might not be NK-specific since irrelevant cells also affected parasite growth <it>in vitro</it>.</p> <p>Conclusions</p> <p>Although NK92 cells are here shown to behave as poor models for the NK immune response against parasites, the results obtained in this study may be of use for future investigations regarding host-parasites interactions in malaria.</p

Immunität gegen Malaria: Einsichten in die Mechanismen hinter Effektor-Funktionen von NK-Zellen

Malaria is a one of the major life-threatening infections worldwide causing thousands of deaths every year. Natural killer cells are thought to play a role in innate responses against Plasmodium falciparum although the means by which such responses occur are still not fully clear. In this thesis, the suitableness of the NK92 cell line as models for general NK cell activation by P. falciparum-infected red blood cells was analyzed to better understand the mechanisms behind NK sensing and responding to parasites. Aiming to cover the current lack of information regarding the impact of P. falciparum on NK cells in a transcriptional level, the gene expression profile of 3 healthy donors’ primary NK cells that were co-cultured with P. falciparum-iRBCs was examined and the expression pattern was compared to the same NK cells following stimulation with IL-12/IL-18. The results demonstrate that NK92 cells have an impact on parasitemia but are not evidently activated by iRBCs although showing transcriptional signs of priming and proliferation upon co-culture. Analysis of the stimulated primary NK cells showed a very similar pattern of gene regulation among all donors. Parasites modulated genes especially involved in the IFN-alpha/-beta arm of the “Interferon Signaling” and other essential molecules in antimicrobial response. IL12/IL18-treated NK cells showed a complete different gene signature: here IFN-gamma and TREM-1-related genes were over-expressed. These findings show that, although NK92 appear to influence parasite growth, the lack of clear signs of activation and response disqualifies such cells as models for the NK response to parasites. In addition, P. falciparum and IL12/IL18 appear to impose diverse imprints on the transcriptome of human primary NK cells. IFN-alpha-related genes were the prominent molecules induced by parasites and deserve to be further investigated as potential new tools in malaria control.Malaria ist eine der wichtigsten lebensbedrohlichen Infektionen weltweit, die Tausende von Todesfällen pro Jahr verursacht. Natürliche Killerzellen spielen eine Rolle bei der angeborenen Immunantwort gegen Plasmodium falciparum. Allerdings sind die beteiligten Mechanismen immer noch nicht vollständig aufgeklärt. In dieser Arbeit wurde untersucht, inwieweit die NK92-Zelllinie als Modell zur allgemeinen Analyse der NK-Zell-Aktivierung durch P. falciparum-infizierte Erythrozyten geeignet ist, um ein besseres Verständnis der Mechanismen, die das Erkennen und die Reaktion auf Parasiten durch NK-Zellen bewirken. Mit dem Ziel ein tieferes Verständnis über die Auswirkungen von P. falciparum auf NK-Zellen auf transkriptioneller Ebene zu erlangen, wurden Genexpressionsprofile von primären NK-Zellen 3 gesunder Spender untersucht, die mit P. falciparum-iRBCs kokultiviert wurden, und mit den Expressionsmustern von IL-12/IL-18 stimulierten NK-Zellen verglichen. Die Ergebnisse zeigten, dass NK92-Zellen einen Einfluss auf die Parasitämie haben, aber offensichtlich nicht von iRBCs aktiviert werden, obwohl auf transkriptioneller Ebene Anzeichen von Aktivierung und Proliferation nach der Kokultur mit iRBC sichtbar wurden. Die stimulierten primären NK-Zellen wiesen ein sehr ähnliches Genregulationsmuster bei allen Spendern auf. So konnte gezeigt werden, dass die Parasiten vor allem Gene modulieren, die durch IFN-alpha/-beta reguliert werden sowie weitere wichtige Moleküle, die an antimikrobiellen Reaktionen beteiligt sind. IL-12/IL-18-behandelte NK-Zellen hingegen zeigten eine ganz andere Gensignatur: hier wurden IFN-gamma- und TREM-1-gesteuerte Genen überexprimiert. Diese Ergebnisse deuten darauf hin, dass, obwohl NK92 scheinbar das Parasitenwachstum beeinflussen, aufgrund der Abwesenheit von klaren Anzeichen einer Aktivierung, NK92 als Modellsystem zur Untersuchung der NK-Zellreaktion auf Parasiten ungeeignet sind. Darüber hinaus scheinen P. falciparum-iRBC und IL-12/IL-18 unterschiedliche Auswirkungen auf das Transkriptom von primären humanen NK-Zellen zu haben. IFN-alpha-gesteuerte Gene erwiesen sich als die von Parasiten primär induzierten Moleküle und sollten deswegen in der Zukunft weiter hinsichtlich ihres potenziellen Einsatzes in der Malariakontrolle untersucht werden

Investigaçao de lectina ligante de manose (MBL) em pacientes com doença celíaca

Orientadora : Iara Taborda de Messias ReasonCo-orientadora: Shirley Ramos da Rosa UtiyamaInclui apendiceDissertaçao (mestrado) - Universidade Federal do Paraná, Setor de Ciencias da Saúde, Programa de Pós-Graduaçao em Ciencias Farmaceuticas. Defesa: Curitiba, 2006Inclui bibliografia e anexoÁrea de concentraçao: Análises clínica

Plasmodium falciparum-infected erythrocytes and IL-12/IL-18 induce diverse transcriptomes in human NK cells: IFN-α/β pathway versus TREM signaling.

The protective immunity of natural killer (NK) cells against malarial infections is thought to be due to early production of type II interferon (IFN) and possibly direct NK cell cytotoxicity. To better understand this mechanism, a microarray analysis was conducted on NK cells from healthy donors PBMCs that were co-cultured with P. falciparum 3D7-infected erythrocytes. A very similar pattern of gene expression was observed among all donors for each treatment in three replicas. Parasites particularly modulated genes involved in IFN-α/β signaling as well as molecules involved in the activation of interferon regulatory factors, pathways known to play a role in the antimicrobial immune response. This pattern of transcription was entirely different from that shown by NK cells treated with IL-12 and IL-18, in which IFN-γ- and TREM-1-related genes were over-expressed. These results suggest that P. falciparum parasites and the cytokines IL-12 and IL-18 have diverse imprints on the transcriptome of human primary NK cells. IFN-α-related genes are the prominent molecules induced by parasites on NK cells and arise as candidate biomarkers that merit to be further investigated as potential new tools in malaria control

NEOTROPICAL XENARTHRANS: a data set of occurrence of xenarthran species in the Neotropics

Xenarthrans—anteaters, sloths, and armadillos—have essential functions for ecosystem maintenance, such as insect control and nutrient cycling, playing key roles as ecosystem engineers. Because of habitat loss and fragmentation, hunting pressure, and conflicts with domestic dogs, these species have been threatened locally, regionally, or even across their full distribution ranges. The Neotropics harbor 21 species of armadillos, 10 anteaters, and 6 sloths. Our data set includes the families Chlamyphoridae (13), Dasypodidae (7), Myrmecophagidae (3), Bradypodidae (4), and Megalonychidae (2). We have no occurrence data on Dasypus pilosus (Dasypodidae). Regarding Cyclopedidae, until recently, only one species was recognized, but new genetic studies have revealed that the group is represented by seven species. In this data paper, we compiled a total of 42,528 records of 31 species, represented by occurrence and quantitative data, totaling 24,847 unique georeferenced records. The geographic range is from the southern United States, Mexico, and Caribbean countries at the northern portion of the Neotropics, to the austral distribution in Argentina, Paraguay, Chile, and Uruguay. Regarding anteaters, Myrmecophaga tridactyla has the most records (n = 5,941), and Cyclopes sp. have the fewest (n = 240). The armadillo species with the most data is Dasypus novemcinctus (n = 11,588), and the fewest data are recorded for Calyptophractus retusus (n = 33). With regard to sloth species, Bradypus variegatus has the most records (n = 962), and Bradypus pygmaeus has the fewest (n = 12). Our main objective with Neotropical Xenarthrans is to make occurrence and quantitative data available to facilitate more ecological research, particularly if we integrate the xenarthran data with other data sets of Neotropical Series that will become available very soon (i.e., Neotropical Carnivores, Neotropical Invasive Mammals, and Neotropical Hunters and Dogs). Therefore, studies on trophic cascades, hunting pressure, habitat loss, fragmentation effects, species invasion, and climate change effects will be possible with the Neotropical Xenarthrans data set. Please cite this data paper when using its data in publications. We also request that researchers and teachers inform us of how they are using these data