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Dive into the research topics where Natacha Lays is active.

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Featured researches published by Natacha Lays.


American Journal of Respiratory Cell and Molecular Biology | 2013

Hemozoin Induces Lung Inflammation and Correlates with Malaria-Associated Acute Respiratory Distress Syndrome

Katrien Deroost; Ariane Tyberghein; Natacha Lays; Sam Noppen; Evelin Schwarzer; Els Vanstreels; Mina Komuta; Mauro Prato; Jing-wen Lin; Ana Pamplona; Chris J. Janse; Paolo Arese; Tania Roskams; Dirk Daelemans; Ghislain Opdenakker; Philippe E. Van den Steen

Malaria-associated acute respiratory distress syndrome (MA-ARDS) is a deadly complication of malaria, and its pathophysiology is insufficiently understood. Both in humans and in murine models, MA-ARDS is characterized by marked pulmonary inflammation. We investigated the role of hemozoin in MA-ARDS in C57Bl/6 mice infected with Plasmodium berghei NK65, P. berghei ANKA, and P. chabaudi AS. By quantifying hemozoin in the lungs and measuring the disease parameters of MA-ARDS, we demonstrated a highly significant correlation between pulmonary hemozoin concentrations, lung weights, and alveolar edema. Histological analysis of the lungs demonstrated that hemozoin is localized in phagocytes and infected erythrocytes, and only occasionally in granulocytes. Species-specific differences in hemozoin production, as measured among individual schizonts, were associated with variations in pulmonary pathogenicity. Furthermore, both pulmonary hemozoin and lung pathology were correlated with the number of infiltrating inflammatory cells, an increased pulmonary expression of cytokines, chemokines, and enzymes, and concentrations of alveolar vascular endothelial growth factor. The causal relationship between hemozoin and inflammation was investigated by injecting P. falciparum-derived hemozoin intravenously into malaria-free mice. Hemozoin potently induced the pulmonary expression of proinflammatory chemokines (interferon-γ inducible protein-10/CXC-chemokine ligand (CXCL)10, monocyte chemotactic protein-1/CC-chemokine ligand 2, and keratinocyte-derived chemokine/CXCL1), cytokines (IL-1β, IL-6, IL-10, TNF, and transforming growth factor-β), and other inflammatory mediators (inducible nitric oxide synthase, heme oxygenase-1, nicotinamide adenine dinucleotide phosphate- oxidase-2, and intercellular adhesion molecule-1). Thus, hemozoin correlates with MA-ARDS and induces pulmonary inflammation.


PLOS ONE | 2011

Insufficiently defined genetic background confounds phenotypes in transgenic studies as exemplified by malaria infection in Tlr9 knockout mice.

Nathalie Geurts; Erik Martens; Sebastien Verhenne; Natacha Lays; Greet Thijs; Stefan Magez; Bénédicte Cauwe; Sandra Li; Hubertine Heremans; Ghislain Opdenakker; Philippe E. Van den Steen

The use of genetically modified mice, i.e. transgenic as well as gene knockout (KO) and knock-in mice, has become an established tool to study gene function in many animal models for human diseases . However, a gene functions in a particular genomic context. This implies the importance of a well-defined homogenous genetic background for the analysis and interpretation of phenotypes associated with genetic mutations. By studying a Plasmodium chabaudi chabaudi AS (PcAS) malaria infection in mice bearing a TLR9 null mutation, we found an increased susceptibility to infection, i.e. higher parasitemia levels and increased mortality. However, this was not triggered by the deficient TLR9 gene itself. Instead, this disease phenotype was dependent on the heterogeneous genetic background of the mice, which appeared insufficiently defined as determined by single nucleotide polymorphism (SNP) analysis. Hence, it is of critical importance to study gene KO phenotypes on a homogenous genetic background identical to that of their wild type (WT) control counterparts. In particular, to avoid problems related to an insufficiently defined genetic background, we advocate that for each study involving genetically modified mice, at least a detailed description of the origin and genetic background of both the WT control and the altered strain of mice is essential.


PLOS ONE | 2015

Altered Lipid Composition of Surfactant and Lung Tissue in Murine Experimental Malaria-Associated Acute Respiratory Distress Syndrome

Diletta Scaccabarozzi; Katrien Deroost; Natacha Lays; Fausta Omodeo Salè; Philippe E. Van den Steen; Donatella Taramelli

Malaria-associated acute lung injury (MA-ALI) and its more severe form malaria-associated acute respiratory distress syndrome (MA-ARDS) are common, often fatal complications of severe malaria infections. However, little is known about their pathogenesis. In this study, biochemical alterations of the lipid composition of the lungs were investigated as possible contributing factors to the severity of murine MA-ALI/ARDS. C57BL/6J mice were infected with Plasmodium berghei NK65 to induce lethal MA-ARDS, or with Plasmodium chabaudi AS, a parasite strain that does not induce lung pathology. The lipid profile of the lung tissue from mice infected with Plasmodium berghei NK65 developing MA-ALI/ARDS, but not that from mice without lung pathology or controls, was characterized by high levels of phospholipids -mainly phosphatidylcholine- and esterified cholesterol. The high levels of polyunsaturated fatty acids and the linoleic/oleic fatty acid ratio of the latter reflect the fatty acid composition of plasma cholesterol esters. In spite of the increased total polyunsaturated fatty acid pool, which augments the relative oxidability of the lung membranes, and the presence of hemozoin, a known pro-oxidant, no excess oxidative stress was detected in the lungs of Plasmodium berghei NK65 infected mice. The bronchoalveolar lavage (BAL) fluid of Plasmodium berghei NK65 infected mice was characterized by high levels of plasma proteins. The phospholipid profile of BAL large and small aggregate fractions was also different from uninfected controls, with a significant increase in the amounts of sphingomyelin and lysophosphatidylcholine and the decrease in phosphatidylglycerol. Both the increase of proteins and lysophosphatidylcholine are known to decrease the intrinsic surface activity of surfactant. Together, these data indicate that an altered lipid composition of lung tissue and BAL fluid, partially ascribed to oedema and lipoprotein infiltration, is a characteristic feature of murine MA-ALI/ARDS and possibly contribute to lung dysfunction.


Malaria Journal | 2018

Differential induction of malaria liver pathology in mice infected with Plasmodium chabaudi AS or Plasmodium berghei NK65

Diletta Scaccabarozzi; Katrien Deroost; Yolanda Corbett; Natacha Lays; Paola Antonia Corsetto; Fausta Omodeo Salè; Philippe E. Van den Steen; Donatella Taramelli

BackgroundCerebral malaria and severe anaemia are the most common deadly complications of malaria, and are often associated, both in paediatric and adult patients, with hepatopathy, whose pathogenesis is not well characterized, and sometimes also with acute respiratory distress syndrome (ARDS). Here, two species of murine malaria, the lethal Plasmodium berghei strain NK65 and self-healing Plasmodium chabaudi strain AS which differ in their ability to cause hepatopathy and/or ARDS were used to investigate the lipid alterations, oxidative damage and host immune response during the infection in relation to parasite load and accumulation of parasite products, such as haemozoin.MethodsPlasma and livers of C57BL/6J mice injected with PbNK65 or PcAS infected erythrocytes were collected at different times and tested for parasitaemia, content of haemozoin and expression of tumour necrosis factor (TNF). Hepatic enzymes, antioxidant defenses and lipids content and composition were also evaluated.ResultsIn the livers of P. berghei NK65 infected mice both parasites and haemozoin accumulated to a greater extent than in livers of P. chabaudi AS infected mice although in the latter hepatomegaly was more prominent. Hepatic enzymes and TNF were increased in both models. Moreover, in P. berghei NK65 infected mice, increased lipid peroxidation, accumulation of triglycerides, impairment of anti-oxidant enzymes and higher collagen deposition were detected. On the contrary, in P. chabaudi AS infected mice the antioxidant enzymes and the lipid content and composition were normal or even lower than uninfected controls.ConclusionsThis study demonstrates that in C57BL/6J mice, depending on the parasite species, malaria-induced liver pathology results in different manifestations, which may contribute to the different outcomes. In P. berghei NK65 infected mice, which concomitantly develop lethal acute respiratory distress syndrome, the liver tissue is characterized by an excess oxidative stress response and reduced antioxidant defenses while in P. chabaudi AS infected mice hepatopathy does not lead to lipid alterations or reduction of antioxidant enzymes, but rather to inflammation and cytokine burst, as shown earlier, that may favour parasite killing and clearance of the infection. These results may help understanding the different clinical profiles described in human malaria hepatopathy.


Nature Communications | 2018

Adrenal hormones mediate disease tolerance in malaria

Leen Vandermosten; Thao-Thy Pham; Sofie Knoops; Charlotte De Geest; Natacha Lays; Kristof Van der Molen; Christopher J. Kenyon; Manu Verma; Karen E. Chapman; Frans Schuit; Karolien De Bosscher; Ghislain Opdenakker; Philippe E. Van den Steen

Malaria reduces host fitness and survival by pathogen-mediated damage and inflammation. Disease tolerance mechanisms counter these negative effects without decreasing pathogen load. Here, we demonstrate that in four different mouse models of malaria, adrenal hormones confer disease tolerance and protect against early death, independently of parasitemia. Surprisingly, adrenalectomy differentially affects malaria-induced inflammation by increasing circulating cytokines and inflammation in the brain but not in the liver or lung. Furthermore, without affecting the transcription of hepatic gluconeogenic enzymes, adrenalectomy causes exhaustion of hepatic glycogen and insulin-independent lethal hypoglycemia upon infection. This hypoglycemia is not prevented by glucose administration or TNF-α neutralization. In contrast, treatment with a synthetic glucocorticoid (dexamethasone) prevents the hypoglycemia, lowers cerebral cytokine expression and increases survival rates. Overall, we conclude that in malaria, adrenal hormones do not protect against lung and liver inflammation. Instead, they prevent excessive systemic and brain inflammation and severe hypoglycemia, thereby contributing to tolerance.Disease tolerance mechanisms counter the negative effects of infection without decreasing the pathogen load. Here, the authors show that in mouse models of malaria, such disease tolerance can be conferred by adrenal hormones, by preventing excessive inflammation and hypoglycemia.


Malaria Journal | 2012

Lipid profile modifications of the lung tissue and surfactant in a murine model of malaria associated ARDS

Diletta Scaccabarozzi; Natacha Lays; Lucia Cortelezzi; Philippe E. Van den Steen; Ghislain Opdenakker; Donatella Taramelli; Fausta Omodeo-Salè

An increase in the total content of PL of BAL in all the infected groups from day 8 post infection and increased levels of total proteins from days 6, were observed. Unexpectedly, the percentage of LA is significantly increased in NK65 mice as well the protein content and protein/PL ratio. These alterations are absent in the AS groups. The LA fraction of the NK65 shows a significant increase in the relative amounts of sphingomyeline and decrease of phosphatidilglycerol. The same changes were observed in the SA fraction accompanied by significant increase of lysophosphatidylcholine (LPC). The membrane enriched fractions of the lungs from NK65 mice are characterized by a significant increase of phosphatidylcholine and phosphatidylethanolamine. No differences are present in the other classes of PL and in the AS group. Conclusions The increase in PL in the lung tissue is ac ommon response to alveolar inflammation. This modification, absent in AS mice, appears to be correlated with malaria ARDS and consistent with the eosinophilic hyaline membrane deposition and cell infiltration observed in the alveoli of NK65 mice. The BAL fluid of NK65 mice is characterized by high increase of protein levels indicative of oedema and alveolar leakage due to the lung pathology. On the contrary, the total PL increase present also in AS groups, seems related to malaria infection but not to lung pathology. Increased total protein levels are present in the LA fraction of NK65 mice, probably due to blood-derived proteins being incorporated into or associated with these microstructures in the alveolar hypophase. The increase of LPC, a known inhibitor of surfactant activity, in the SA fraction of NK65 mice is consistent with the action of


Archive | 2016

Endogenous glucocorticoids do not prevent peripheral inflammation but protect from lethal hypoglycaemia

Leen Vandermosten; Charlotte De Geest; Natacha Lays; Sofie Knoops; Karen E. Chapman; Karolien De Bosscher; Ghislain Opdenakker; Philippe E. Van den Steen


Archive | 2016

Pathogenesis of malaria-associated acute respiratory distress syndrome, a major deadly complication of malaria

Philippe E. Van den Steen; Thy Pham; Katrien Deroost; Natacha Lays; Mina Komuta; Evelin Schwarzer; Chris J. Janse; Ghislain Opdenakker


Archive | 2016

Improved method for quantification of malaria parasite sequestration in tissues

Thy Pham; Sigrid D'Haese; Evelien Van Herck; Natacha Lays; Nele Berghmans; Chris J. Janse; Ghislain Opdenakker; Philippe E. Van den Steen


Archive | 2016

Endogenous glucocorticoids protect against lethal hypoglycemia and brain inflammation in two mouse models of malaria

Leen Vandermosten; Charlotte De Geest; Natacha Lays; Sofie Knoops; Karen E. Chapman; Ghislain Opdenakker; Philippe E. Van den Steen

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Philippe E. Van den Steen

Rega Institute for Medical Research

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Ghislain Opdenakker

Rega Institute for Medical Research

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Katrien Deroost

Rega Institute for Medical Research

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Chris J. Janse

Leiden University Medical Center

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Leen Vandermosten

Rega Institute for Medical Research

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Sofie Knoops

Rega Institute for Medical Research

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