179 results on '"Moll, Kirsten"'
Search Results
2. Targeted plasma proteomics reveals signatures discriminating COVID-19 from sepsis with pneumonia
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Palma Medina, Laura M., Babačić, Haris, Dzidic, Majda, Parke, Åsa, Garcia, Marina, Maleki, Kimia T., Unge, Christian, Lourda, Magda, Kvedaraite, Egle, Chen, Puran, Muvva, Jagadeeswara Rao, Cornillet, Martin, Emgård, Johanna, Moll, Kirsten, Michaëlsson, Jakob, Flodström-Tullberg, Malin, Brighenti, Susanna, Buggert, Marcus, Mjösberg, Jenny, Malmberg, Karl-Johan, Sandberg, Johan K., Gredmark-Russ, Sara, Rooyackers, Olav, Svensson, Mattias, Chambers, Benedict J., Eriksson, Lars I., Pernemalm, Maria, Björkström, Niklas K., Aleman, Soo, Ljunggren, Hans-Gustaf, Klingström, Jonas, Strålin, Kristoffer, and Norrby-Teglund, Anna
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- 2023
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3. High-dimensional profiling reveals phenotypic heterogeneity and disease-specific alterations of granulocytes in COVID-19
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Karolinska KI/K COVID-19 Study Group, Lourda, Magda, Dzidic, Majda, Hertwig, Laura, Bergsten, Helena, Medina, Laura M. Palma, Sinha, Indranil, Kvedaraite, Egle, Chen, Puran, Muvva, Jagadeeswara R., Gorin, Jean-Baptiste, Cornillet, Martin, Emgård, Johanna, Moll, Kirsten, García, Marina, Maleki, Kimia T., Klingström, Jonas, Michaëlsson, Jakob, Flodström-Tullberg, Malin, Brighenti, Susanna, Buggert, Marcus, Mjösberg, Jenny, Malmberg, Karl-Johan, Sandberg, Johan K., Henter, Jan-Inge, Folkesson, Elin, Gredmark-Russ, Sara, Sönnerborg, Anders, Eriksson, Lars I., Rooyackers, Olav, Aleman, Soo, Strålin, Kristoffer, Ljunggren, Hans-Gustaf, Björkström, Niklas K., Svensson, Mattias, Ponzetta, Andrea, Norrby-Teglund, Anna, and Chambers, Benedict J.
- Published
- 2021
4. Streptokinase reduces Streptococcus dysgalactiae subsp. equisimilis biofilm formation.
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Tölken, Lea A., Neufend, Janine V., Oppegaard, Oddvar, Methling, Karen, Moll, Kirsten, Redanz, Sylvio, Katsburg, Miriam M.D., Ali, Murtadha Q., Shumba, Patience, Kreikemeyer, Bernd, Skrede, Steinar, Fulde, Marcus, Norrby-Teglund, Anna, Lalk, Michael, Kittang, Bård R., and Siemens, Nikolai
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SOFT tissue infections ,STREPTOCOCCAL diseases ,STREPTOCOCCUS pyogenes ,STREPTOKINASE ,COMORBIDITY - Abstract
Background: Streptococcus dysgalactiae subspecies equisimilis (SDSE) is increasingly recognized as an emerging cause of invasive diseases including necrotizing soft tissue infections (NSTIs). In contrast to the closely related Streptococcus pyogenes, SDSE infections mainly affect older and comorbid patients. Biofilm formation has been demonstrated in soft tissue biopsies of S. pyogenes NSTI cases. Results: Here, we show that bacterial aggregations indicative of biofilms are also present in SDSE NSTI. Although streptokinase (Ska) activity and biofilm formation did not correlate in a diverse set of clinical SDSE isolates, addition of exogenous Ska at an early time point prevented biofilm formation for selected strains. Deletion of ska in SDSE S118 strain resulted in increased biofilm forming capacity. Ska-deficient mutant strain was characterized by a higher metabolic activity and consequent metabolome profiling of biofilms identified higher deposition of a wide range of metabolites as compared to the wild-type. Conclusions: Our results argue that Ska suppresses biofilm formation in SDSE independent of its original plasminogen converting activity. However, the impact of biofilms and its consequences for patient outcomes in streptococcal NSTIs remain to be elucidated. [ABSTRACT FROM AUTHOR]
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- 2024
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5. Intestinal stroma guides monocyte differentiation to macrophages through GM-CSF.
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Kvedaraite, Egle, Lourda, Magda, Mouratidou, Natalia, Düking, Tim, Padhi, Avinash, Moll, Kirsten, Czarnewski, Paulo, Sinha, Indranil, Xagoraris, Ioanna, Kokkinou, Efthymia, Damdimopoulos, Anastasios, Weigel, Whitney, Hartwig, Olga, Santos, Telma E., Soini, Tea, Van Acker, Aline, Rahkonen, Nelly, Flodström Tullberg, Malin, Ringqvist, Emma, and Buggert, Marcus
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MONOCYTES ,INFLAMMATORY bowel diseases ,GRANULOCYTE-macrophage colony-stimulating factor ,MACROPHAGES ,INTESTINES ,STROMAL cells ,HOMEOSTASIS - Abstract
Stromal cells support epithelial cell and immune cell homeostasis and play an important role in inflammatory bowel disease (IBD) pathogenesis. Here, we quantify the stromal response to inflammation in pediatric IBD and reveal subset-specific inflammatory responses across colon segments and intestinal layers. Using data from a murine dynamic gut injury model and human ex vivo transcriptomic, protein and spatial analyses, we report that PDGFRA
+ CD142− /low fibroblasts and monocytes/macrophages co-localize in the intestine. In primary human fibroblast-monocyte co-cultures, intestinal PDGFRA+ CD142− /low fibroblasts foster monocyte transition to CCR2+ CD206+ macrophages through granulocyte-macrophage colony-stimulating factor (GM-CSF). Monocyte-derived CCR2+ CD206+ cells from co-cultures have a phenotype similar to intestinal CCR2+ CD206+ macrophages from newly diagnosed pediatric IBD patients, with high levels of PD-L1 and low levels of GM-CSF receptor. The study describes subset-specific changes in stromal responses to inflammation and suggests that the intestinal stroma guides intestinal macrophage differentiation. Stromal cells are key players in immune cell homeostasis. Here, the authors decipher subset-specific human stromal responses in inflammatory bowel disease and suggest that intestinal PDGFRA+ CD142− /low fibroblasts guide monocyte transition to macrophages in human gut through GM-CSF. [ABSTRACT FROM AUTHOR]- Published
- 2024
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6. Survival of P. falciparum infected red blood cell aggregates in elongational shear flow.
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Jötten, Anna M., Schepp, Anabelle, Machon, Adam, Moll, Kirsten, Wahlgren, Mats, Krüger, Timm, and Westerhausen, Christoph
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ERYTHROCYTES ,SHEAR flow ,BLOOD groups ,HEMATOPOIESIS ,ERYTHROCYTE deformability ,BLOOD group antigens ,CELL aggregation ,PROTEIN binding - Abstract
Rosetting, the formation of red blood cell aggregates, is a life-threatening condition in malaria tropica and not yet fully understood. We study rosette stability using a set of microfluidic stenotic channels, with varied narrowing angle and erythrocytes of blood groups O and A. We find reduced ability of a rosette to pass a stenosis without disruption, the longer the tapered part of the constriction and the narrower the stenosis is. In general, this ability increases with rosette size and is 5–15% higher in blood group A. The experimental results are substantiated by equivalent experiments using lectin-induced red blood cell aggregates and a simulation of the underlying protein binding kinetics. [ABSTRACT FROM AUTHOR]
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- 2024
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7. Antibiotics against Pseudomonas aeruginosa on Human Skin Cell Lines: Determination of the Highest Non-Cytotoxic Concentrations with Antibiofilm Capacity for Wound Healing Strategies.
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Quiñones-Vico, María I., Fernández-González, Ana, Ubago-Rodríguez, Ana, Moll, Kirsten, Norrby-Teglund, Anna, Svensson, Mattias, Gutiérrez-Fernández, José, Torres, Jesús M., and Arias-Santiago, Salvador
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CELL determination ,WOUND healing ,ANTIBIOTICS ,CELL lines ,ARTIFICIAL skin ,ANTIBACTERIAL agents ,PSEUDOMONAS aeruginosa - Abstract
Pseudomonas aeruginosa is one of the most common microorganisms causing infections of severe skin wounds. Antibiotic or antiseptic treatments are crucial to prevent and curb these infections. Antiseptics have been reported to be cytotoxic to skin cells and few studies evaluate the impact of commonly used antibiotics. This study evaluates how clinical antibiotics affect skin cells' viability, proliferation, migration, and cytokine secretion and defines the highest non-cytotoxic concentrations that maintain antibacterial activity. Cell proliferation, viability, and migration were evaluated on cell monolayers. Cytokines related to the wound healing process were determined. The minimum inhibitory concentrations and the impact on bacterial biofilm were assessed. Results showed that 0.02 mg/mL ciprofloxacin and 1 mg/mL meropenem are the highest non-cytotoxic concentrations for fibroblasts and keratinocytes while 1.25 mg/mL amikacin and 0.034 mg/mL colistin do not affect fibroblasts' viability and cytokine secretion but have an impact on keratinocytes. These concentrations are above the minimum inhibitory concentration but only amikacin could eradicate the biofilm. For the other antibiotics, cytotoxic concentrations are needed to eradicate the biofilm. Combinations with colistin at non-cytotoxic concentrations effectively eliminate the biofilm. These results provide information about the concentrations required when administering topical antibiotic treatments on skin lesions, and how these antibiotics affect wound management therapies. This study set the basis for the development of novel antibacterial wound healing strategies such as antibiotic artificial skin substitutes. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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8. Development of drug-loaded immunoliposomes for the selective targeting and elimination of rosetting Plasmodium falciparum-infected red blood cells
- Author
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Moles, Ernest, Moll, Kirsten, Ch'ng, Jun-Hong, Parini, Paolo, Wahlgren, Mats, and Fernàndez-Busquets, Xavier
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- 2016
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9. Additional file 1 of Neutrophil-derived reactive agents induce a transient SpeB negative phenotype in Streptococcus pyogenes
- Author
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Shumba, Patience, Sura, Thomas, Moll, Kirsten, Chakrakodi, Bhavya, Tölken, Lea A., Hoßmann, Jörn, Hoff, Katharina J., Hyldegaard, Ole, Nekludov, Michael, Svensson, Mattias, Arnell, Per, Skrede, Steinar, Norrby-Teglund, Anna, and Siemens, Nikolai
- Abstract
Additional file 1. Figures S1-S16 and methods section.
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- 2023
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10. RIFINs are adhesins implicated in severe Plasmodium falciparum malaria
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Goel, Suchi, Palmkvist, Mia, Moll, Kirsten, Joannin, Nicolas, Lara, Patricia, Akhouri, Reetesh R., Moradi, Nasim, Ojemalm, Karin, Westman, Mattias, Angeletti, Davide, Kjellin, Hanna, Lehtio, Janne, Blixt, Ola, Idestrom, Lars, Gahmberg, Carl G., Storry, Jill R., Hult, Annika K., Olsson, Martin L., von Heijne, Gunnar, Nilsson, IngMarie, and Wahlgren, Mats
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Erythrocytes -- Physiological aspects ,Malaria -- Development and progression -- Risk factors ,Plasmodium falciparum -- Health aspects ,Biological sciences ,Health - Abstract
Rosetting is a virulent Plasmodium falciparum phenomenon associated with severe malaria. Here we demonstrate that P falciparum-encoded repetitive interspersed families of polypeptides (RIFINs) are expressed on the surface of infected red blood cells (iRBCs), bind to RBCs--preferentially of blood group A--to form large rosettes and mediate microvascular binding of iRBCs. We suggest that RIFINs have a fundamental role in the development of severe malaria and thereby contribute to the varying global distribution of ABO blood groups in the human population., Sequestration and rosetting in individuals with severe Plasmodium falciparum malaria has been attributed to P. falciparum erythrocyte membrane protein 1 (PfEMP1) (1-8). However, antibodies to PfEMP1 disrupt rosettes of parasites [...]
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- 2015
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11. PfEMP1-DBL1α Amino Acid Motifs in Severe Disease States of Plasmodium falciparum Malaria
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Normark, Johan, Nilsson, Daniel, Ribacke, Ulf, Winter, Gerhard, Moll, Kirsten, Wheelock, Craig E., Bayarugaba, Justus, Kironde, Fred, Egwang, Thomas G., Chen, Qijun, Andersson, Björn, and Wahlgren, Mats
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- 2007
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12. High-dimensional profiling reveals phenotypic heterogeneity and disease-specific alterations of granulocytes in COVID-19
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Lourda, Magda, Dzidic, Majda, Hertwig, Laura, Bergsten, Helena, Palma Medina, Laura M., Sinha, Indranil, Kvedaraite, Egle, Chen, Puran, Muvva, Jagadeeswara R., Gorin, Jean-Baptiste, Cornillet, Martin, Emgård, Johanna, Moll, Kirsten, García, Marina, Maleki, Kimia T., Klingström, Jonas, Michaëlsson, Jakob, Flodström-Tullberg, Malin, Brighenti, Susanna, Buggert, Marcus, Mjösberg, Jenny, Malmberg, Karl-Johan, Sandberg, Johan K., Henter, Jan-Inge, Folkesson, Elin, Gredmark-Russ, Sara, Sönnerborg, Anders, Eriksson, Lars I., Rooyackers, Olav, Aleman, Soo, Strålin, Kristoffer, Ljunggren, Hans-Gustaf, Björkström, Niklas K., Svensson, Mattias, Ponzetta, Andrea, Norrby-Teglund, Anna, and Chambers, Benedict J.
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Organ Dysfunction Scores ,SARS-CoV-2 ,COVID-19 ,Biological Sciences ,viral immune responses ,Models, Biological ,Severity of Illness Index ,high-dimensional flow cytometry ,Immunity, Innate ,Immunophenotyping ,Leukocyte Count ,Immunology and Inflammation ,eosinophil and basophil activation ,neutrophil heterogeneity ,Humans ,Lung ,Granulocytes - Abstract
Significance Accumulating evidence shows that granulocytes are key modulators of the immune response to SARS-CoV-2 infection, and their dysregulation could significantly impact COVID-19 severity and patient recovery after virus clearance. In the present study, we identify selected immune traits in neutrophil, eosinophil, and basophil subsets associated with severity of COVID-19 and with peripheral protein profiles. Moreover, computational modeling indicates that the combined use of phenotypic data and laboratory measurements can effectively predict key clinical outcomes in COVID-19 patients. Finally, patient-matched longitudinal analysis shows phenotypic normalization of granulocyte subsets 4 mo after hospitalization. Overall, in this work, we extend the current understanding of the distinct contribution of granulocyte subsets to COVID-19 pathogenesis., Since the outset of the COVID-19 pandemic, increasing evidence suggests that the innate immune responses play an important role in the disease development. A dysregulated inflammatory state has been proposed as a key driver of clinical complications in COVID-19, with a potential detrimental role of granulocytes. However, a comprehensive phenotypic description of circulating granulocytes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)−infected patients is lacking. In this study, we used high-dimensional flow cytometry for granulocyte immunophenotyping in peripheral blood collected from COVID-19 patients during acute and convalescent phases. Severe COVID-19 was associated with increased levels of both mature and immature neutrophils, and decreased counts of eosinophils and basophils. Distinct immunotypes were evident in COVID-19 patients, with altered expression of several receptors involved in activation, adhesion, and migration of granulocytes (e.g., CD62L, CD11a/b, CD69, CD63, CXCR4). Paired sampling revealed recovery and phenotypic restoration of the granulocytic signature in the convalescent phase. The identified granulocyte immunotypes correlated with distinct sets of soluble inflammatory markers, supporting pathophysiologic relevance. Furthermore, clinical features, including multiorgan dysfunction and respiratory function, could be predicted using combined laboratory measurements and immunophenotyping. This study provides a comprehensive granulocyte characterization in COVID-19 and reveals specific immunotypes with potential predictive value for key clinical features associated with COVID-19.
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- 2021
13. Genetic diversity of Plasmodium falciparum infections in mild and severe malaria of children from Kampala, Uganda
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Kiwuwa, Mpungu Steven, Ribacke, Ulf, Moll, Kirsten, Byarugaba, Justus, Lundblom, Klara, Färnert, Anna, Fred, Kironde, and Wahlgren, Mats
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- 2013
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14. Additional file 1 of Red blood cell blood group A antigen level affects the ability of heparin and PfEMP1 antibodies to disrupt Plasmodium falciparum rosettes
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Hedberg, Pontus, Sirel, Madle, Moll, Kirsten, Kiwuwa, Mpungu Steven, H��glund, Petter, Ribacke, Ulf, and Wahlgren, Mats
- Abstract
Additional file 1. Supplementary material.
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- 2021
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15. Induction of cross-reactive immune responses to NTS-DBL-1α/x of PfEMP1 and in vivo protection on challenge with Plasmodium falciparum
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Ahuja, Sanjay, Pettersson, Fredrik, Moll, Kirsten, Jonsson, Cathrine, Wahlgren, Mats, and Chen, Qijun
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- 2006
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16. Red blood cell blood group A antigen level affects the ability of heparin and PfEMP1 antibodies to disrupt Plasmodium falciparum rosettes.
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Hedberg, Pontus, Sirel, Madle, Moll, Kirsten, Kiwuwa, Mpungu Steven, Höglund, Petter, Ribacke, Ulf, and Wahlgren, Mats
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BLOOD group antigens ,ERYTHROCYTES ,BLOOD cells ,PLASMODIUM falciparum ,ABO blood group system - Abstract
Background: The histo-blood group ABO system has been associated with adverse outcomes in COVID-19, thromboembolic diseases and Plasmodium falciparum malaria. An integral part of the severe malaria pathogenesis is rosetting, the adherence of parasite infected red blood cells (RBCs) to uninfected RBCs. Rosetting is influenced by the host's ABO blood group (Bg) and rosettes formed in BgA have previously been shown to be more resilient to disruption by heparin and shield the parasite derived surface antigens from antibodies. However, data on rosetting in weak BgA subgroups is scarce and based on investigations of relatively few donors. Methods: An improved high-throughput flow cytometric assay was employed to investigate rosetting characteristics in an extensive panel of RBC donor samples of all four major ABO Bgs, as well as low BgA expressing samples. Results: All non-O Bgs shield the parasite surface antigens from strain-specific antibodies towards P. falciparum erythrocyte membrane protein 1 (PfEMP1). A positive correlation between A-antigen levels on RBCs and rosette tightness was observed, protecting the rosettes from heparin- and antibody-mediated disruption. Conclusions: These results provide new insights into how the ABO Bg system affects the disease outcome and cautions against interpreting the results from the heterogeneous BgA phenotype as a single group in epidemiological and experimental studies. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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17. Enhanced virulence of Plasmodium falciparum in blood of diabetic patients.
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Ch'ng, Jun-Hong, Moll, Kirsten, Wyss, Katja, Hammar, Ulf, Rydén, Mikael, Kämpe, Olle, Färnert, Anna, and Wahlgren, Mats
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PEOPLE with diabetes , *TYPE 2 diabetes , *PLASMODIUM falciparum , *GLYCOSYLATED hemoglobin , *TYPE 1 diabetes , *MALARIA , *CANDIDATUS diseases , *ERYTHROCYTES - Abstract
Rising prevalence of diabetes in sub-Saharan Africa, coupled with continued malaria transmission, has resulted more patients dealing with both communicable and non-communicable diseases. We previously reported that travelers with type 2 diabetes mellitus (T2DM) infected with Plasmodium falciparum were three times more likely to develop severe malaria than non-diabetics. Here we explore the biological basis for this by testing blood from uninfected subjects with type 1 and type 2 diabetes, ex vivo, for their effects on parasite growth and rosetting (binding of infected erythrocytes to uninfected erythrocytes). Rosetting was associated with type 2 diabetes, blood glucose and erythrocyte sedimentation rate (ESR), while parasite growth was positively associated with blood glucose, glycated hemoglobin (HbA1c), body mass index (BMI), fibrinogen and triglycerides. This study establishes a link between diabetes and malaria virulence assays, potentially explaining the protective effect of good glycemic control against severe malaria in subjects with diabetes. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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18. var gene transcription and PfEMP1 expression in the rosetting and cytoadhesive Plasmodium falciparum clone FCR3S1.2
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Chen Qijun, Normark Johan, Blomqvist Karin, Moll Kirsten, Albrecht Letusa, and Wahlgren Mats
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Arctic medicine. Tropical medicine ,RC955-962 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background The pathogenicity of Plasmodium falciparum is in part due to the ability of the parasitized red blood cell (pRBC) to adhere to intra-vascular host cell receptors and serum-proteins. Binding of the pRBC is mediated by Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), a large multi-variant molecule encoded by a family of ≈60 var genes. Methods The study of var gene transcription in the parasite clone FCR3S1.2 was performed by semi-quantitative PCR and quantitative PCR (qPCR). The expression of the major PfEMP1 in FCR3S1.2 pRBC was analysed with polyclonal sera in rosette disruption assays and immunofluorecence. Results Transcripts from var1 (FCR3S1.2var1; IT4var21) and other var genes were detected by semi-quantitative PCR but results from qPCR showed that one var gene transcript dominated over the others (FCR3S1.2var2; IT4var60). Antibodies raised in rats to the recombinant NTS-DBL1α of var2 produced in E. coli completely and dose-dependently disrupted rosettes (≈95% at a dilution of 1/5). The sera reacted with the Maurer's clefts in trophozoite stages (IFA) and to the infected erythrocyte surface (FACS) indicating that FCR3S1.2var2 encodes the dominant PfEMP1 expressed in this parasite. Conclusion The major transcript in the rosetting model parasite FCR3S1.2 is FCR3S1.2var2 (IT4var60). The results suggest that this gene encodes the PfEMP1-species responsible for the rosetting phenotype of this parasite. The activity of previously raised antibodies to the NTS-DBL1α of FCR3S1.2var1 is likely due to cross-reactivity with NTS-DBL1α of the var2 encoded PfEMP1.
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- 2011
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19. Antibodies in children with malaria to PfEMP1, RIFIN and SURFIN expressed at the Plasmodium falciparum parasitized red blood cell surface
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Quintana, Maria del Pilar, Ch'ng, Jun-Hong, Moll, Kirsten, Zandian, Arash, Nilsson, Peter, Idris, Zulkarnain Md, Saiwaew, Somporn, Qundos, Ulrika, Wahlgren, Mats, Quintana, Maria del Pilar, Ch'ng, Jun-Hong, Moll, Kirsten, Zandian, Arash, Nilsson, Peter, Idris, Zulkarnain Md, Saiwaew, Somporn, Qundos, Ulrika, and Wahlgren, Mats
- Abstract
Naturally acquired antibodies to proteins expressed on the Plasmodium falciparum parasitized red blood cell (pRBC) surface steer the course of a malaria infection by reducing sequestration and stimulating phagocytosis of pRBC. Here we have studied a selection of proteins representing three different parasite gene families employing a well-characterized parasite with a severe malaria phenotype (FCR3S1.2). The presence of naturally acquired antibodies, impact on rosetting rate, surface reactivity and opsonization for phagocytosis in relation to different blood groups of the ABO system were assessed in a set of sera from children with mild or complicated malaria from an endemic area. We show that the naturally acquired immune responses, developed during malaria natural infection, have limited access to the pRBCs inside a blood group A rosette. The data also indicate that SURFIN4.2 may have a function at the pRBC surface, particularly during rosette formation, this role however needs to be further validated. Our results also indicate epitopes differentially recognized by rosette-disrupting antibodies on a peptide array. Antibodies towards parasite-derived proteins such as PfEMP1, RIFIN and SURFIN in combination with host factors, essentially the ABO blood group of a malaria patient, are suggested to determine the outcome of a malaria infection., QC 20180405
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- 2018
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20. SURGE complex of Plasmodium falciparum in the rhoptry-neck (SURFIN4.2-RON4-GLURP) contributes to merozoite invasion
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Quintana, Maria del Pilar, Ch'ng, Jun-Hong, Zandian, Arash, Imam, Maryam, Hultenby, Kjell, Theisen, Michael, Nilsson, Peter, Qundos, Ulrika, Moll, Kirsten, Chan, Sherwin, Wahlgren, Mats, Quintana, Maria del Pilar, Ch'ng, Jun-Hong, Zandian, Arash, Imam, Maryam, Hultenby, Kjell, Theisen, Michael, Nilsson, Peter, Qundos, Ulrika, Moll, Kirsten, Chan, Sherwin, and Wahlgren, Mats
- Abstract
Plasmodium falciparum invasion into red blood cells (RBCs) is a complex process engaging proteins on the merozoite surface and those contained and sequentially released from the apical organelles (micronemes and rhoptries). Fundamental to invasion is the formation of a moving junction (MJ), a region of close apposition of the merozoite and the RBC plasma membranes, through which the merozoite draws itself before settling into a newly formed parasitophorous vacuole (PV). SURFIN4.2 was identified at the surface of the parasitized RBCs (pRBCs) but was also found apically associated with the merozoite. Using antibodies against the N-terminus of the protein we show the presence of SURFIN4.2 in the neck of the rhoptries, its secretion into the PV and shedding into the culture supernatant upon schizont rupture. Using immunoprecipitation followed by mass spectrometry we describe here a novel protein complex we have named SURGE where SURFIN4.2 forms interacts with the rhoptry neck protein 4 (RON4) and the Glutamate Rich Protein (GLURP). The N-terminal cysteine-rich domain (CRD) of SURFIN4.2 mediates binding to the RBC membrane and its interaction with RON4 suggests its involvement in the contact between the merozoite apex and the RBC at the MJ. Supporting this suggestion, we also found that polyclonal antibodies to the extracellular domain (including the CRD) of SURFIN4.2 partially inhibit merozoite invasion. We propose that the formation of the SURGE complex participates in the establishment of parasite infection within the PV and the RBCs., QC 20180827
- Published
- 2018
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21. ABO Blood Group Antigen Decorated Giant Unilamellar Vesicles Exhibit Distinct Interactions with Plasmodium falciparum Infected Red Blood Cells
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Vagianou, Charikleia-Despoina, Stuhr-Hansen, Nicolai, Moll, Kirsten, Bovin, Nicolai, Wahlgren, Mats, Blixt, Ola, Vagianou, Charikleia-Despoina, Stuhr-Hansen, Nicolai, Moll, Kirsten, Bovin, Nicolai, Wahlgren, Mats, and Blixt, Ola
- Published
- 2018
22. Blood group and size dependent stability of P. falciparum infected red blood cell aggregates in capillaries.
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Jötten, Anna Martina, Moll, Kirsten, Wahlgren, Mats, Wixforth, Achim, and Westerhausen, Christoph
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ABO blood group system , *BLOOD groups , *ERYTHROCYTES , *GROUP size , *FREQUENCY stability , *CAPILLARIES - Abstract
For Plasmodium falciparum related malaria (B50), one of the outstanding host factors for the development of severe disease is the ABO blood group of malaria patients, where blood group O reduces the probability of severe disease as compared to individuals of groups A, B, or AB. In this report, we investigate the stability of rosette aggregates in malaria caused by Plasmodium falciparum in microflows. These flows are created in microfluidic channels with stenosis-like constrictions of different widths down to ones narrower as the rosette's diameter. High speed videos were recorded and analyzed by a MATLAB© based tracking software (SURF: SUrvival of Rosettes in Flow). We find a correlation of rosette size, channel diameter, and blood group regarding the mobility of the rosettes. Following the concept of a thermodynamic model, we find a critical width of the stenosis for rosette rupture during their passage. Our data reveal that under physiologically relevant conditions, rosettes in blood group A have a higher rosette frequency and stability as compared to blood group O (BG O), which constitutes a crucial factor promoting the observed protection in BG O individuals against severe malaria in non-O individuals. [ABSTRACT FROM AUTHOR]
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- 2020
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23. Epitopes of anti-RIFIN antibodies and characterization of rif-expressing Plasmodium falciparum parasites by RNA sequencing
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Ch'ng, Jun-Hong, Sirel, Madle, Zandian, Arash, Quintana, Maria del Pilar, Chan, Sherwin Chun Leung, Moll, Kirsten, Tellgren-Roth, Asa, Nilsson, IngMarie, Nilsson, Peter, Qundos, Ulrika, Wahlgren, Mats, Ch'ng, Jun-Hong, Sirel, Madle, Zandian, Arash, Quintana, Maria del Pilar, Chan, Sherwin Chun Leung, Moll, Kirsten, Tellgren-Roth, Asa, Nilsson, IngMarie, Nilsson, Peter, Qundos, Ulrika, and Wahlgren, Mats
- Abstract
Variable surface antigens of Plasmodium falciparum have been a major research focus since they facilitate parasite sequestration and give rise to deadly malaria complications. Coupled with its potential use as a vaccine candidate, the recent suggestion that the repetitive interspersed families of polypeptides (RIFINs) mediate blood group A rosetting and influence blood group distribution has raised the research profile of these adhesins. Nevertheless, detailed investigations into the functions of this highly diverse multigene family remain hampered by the limited number of validated reagents. In this study, we assess the specificities of three promising polyclonal anti-RIFIN antibodies that were IgG-purified from sera of immunized animals. Their epitope regions were mapped using a 175,000-peptide microarray holding overlapping peptides of the P. falciparum variable surface antigens. Through immunoblotting and immunofluorescence imaging, we show that different antibodies give varying results in different applications/assays. Finally, we authenticate the antibody-based detection of RIFINs in two previously uncharacterized non-rosetting parasite lines by identifying the dominant rif transcripts using RNA sequencing., QC 20170329
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- 2017
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24. MOESM3 of ARAM: an automated image analysis software to determine rosetting parameters and parasitaemia in Plasmodium samples
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Kudella, Patrick Wolfgang, Moll, Kirsten, Wahlgren, Mats, Wixforth, Achim, and Westerhausen, Christoph
- Abstract
Additional file 3: Figure S3. Bland-Altman diagrams. Left Comparison of the cell detection by ARAM and an operator. Right Comparison of the determined rosette size by ARAM and an operator.
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- 2016
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25. MOESM1 of Phagocytosis-inducing antibodies to Plasmodium falciparum upon immunization with a recombinant PfEMP1 NTS-DBL1α domain
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Quintana, Maria, Angeletti, Davide, Moll, Kirsten, Qijun Chen, and Wahlgren, Mats
- Abstract
Additional file 1: Figure S2. IgG levels in the human samples against the recombinant NTS-DBL1α (ITvar60) measured by ELISA. The original OD values were fitted to a 4 Parameter Logistic (4PL) curve. The antibody concentration is expressed as log of the dilution factor (DF). Immune samples are depicted in red and named from 1 to 6, The pooled immune sample (IMP) is also depicted. Swedish control pool (SCP) is depicted in blue.
- Published
- 2016
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26. SURGE complex of Plasmodium falciparum in the rhoptry-neck (SURFIN4.2-RON4-GLURP) contributes to merozoite invasion.
- Author
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Quintana, Maria del Pilar, Ch’ng, Jun-Hong, Zandian, Arash, Imam, Maryam, Hultenby, Kjell, Theisen, Michael, Nilsson, Peter, Qundos, Ulrika, Moll, Kirsten, Chan, Sherwin, and Wahlgren, Mats
- Subjects
PLASMODIUM falciparum ,ERYTHROCYTES ,MEROZOITES ,ORGANELLES ,CELL membranes - Abstract
Plasmodium falciparum invasion into red blood cells (RBCs) is a complex process engaging proteins on the merozoite surface and those contained and sequentially released from the apical organelles (micronemes and rhoptries). Fundamental to invasion is the formation of a moving junction (MJ), a region of close apposition of the merozoite and the RBC plasma membranes, through which the merozoite draws itself before settling into a newly formed parasitophorous vacuole (PV). SURFIN
4.2 was identified at the surface of the parasitized RBCs (pRBCs) but was also found apically associated with the merozoite. Using antibodies against the N-terminus of the protein we show the presence of SURFIN4.2 in the neck of the rhoptries, its secretion into the PV and shedding into the culture supernatant upon schizont rupture. Using immunoprecipitation followed by mass spectrometry we describe here a novel protein complex we have named SURGE where SURFIN4.2 forms interacts with the rhoptry neck protein 4 (RON4) and the Glutamate Rich Protein (GLURP). The N-terminal cysteine-rich–domain (CRD) of SURFIN4.2 mediates binding to the RBC membrane and its interaction with RON4 suggests its involvement in the contact between the merozoite apex and the RBC at the MJ. Supporting this suggestion, we also found that polyclonal antibodies to the extracellular domain (including the CRD) of SURFIN4.2 partially inhibit merozoite invasion. We propose that the formation of the SURGE complex participates in the establishment of parasite infection within the PV and the RBCs. [ABSTRACT FROM AUTHOR]- Published
- 2018
- Full Text
- View/download PDF
27. Inhibition of merozoite invasion and transient de-sequestration by sevuparin in humans with Plasmodium falciparum malaria.
- Author
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Leitgeb, Anna M., Charunwatthana, Prakaykaew, Rueangveerayut, Ronnatrai, Uthaisin, Chirapong, Silamut, Kamolrat, Chotivanich, Kesinee, Sila, Patima, Moll, Kirsten, Lee, Sue J., Lindgren, Maria, Holmer, Erik, Färnert, Anna, Kiwuwa, Mpungu S., Kristensen, Jens, Herder, Christina, Tarning, Joel, Wahlgren, Mats, and Dondorp, Arjen M.
- Subjects
MEROZOITES ,MALARIA treatment ,SEQUESTRATION (Chemistry) ,PLASMODIUM falciparum ,INTRAVENOUS therapy ,DISEASE exacerbation - Abstract
Severe malaria: Even with the best available treatment, the mortality from severe Plasmodium falciparum malaria remains high. Typical features at death are high parasite loads and obstructed micro- vasculature. Infected erythrocytes (IE) containing mature parasites bind to the host receptor heparan sulfate, which is also an important receptor for merozoite invasion. To block merozoite invasion has not previously been proposed as an adjunctive therapeutic approach but it may preclude the early expansion of an infection that else leads to exacerbated sequestration and death. Sevuparin in phase I study: The drug sevuparin was developed from heparin because heparan sulfate and heparin are nearly identical, so the rationale was that sevuparin would act as a decoy receptor during malaria infection. A phase I study was performed in healthy male volunteers and sevuparin was found safe and well tolerated. Sevuparin in phase I/II clinical study: A phase I/II clinical study was performed in which sevuparin was administered via short intravenous infusions to malaria patients with uncomplicated malaria who were also receiving atovaquone/proguanil treatment. This was a Phase I/II, randomized, open label, active control, parallel assignment study. Sevuparin was safe and well tolerated in the malaria patients. The mean relative numbers of ring-stage IEs decreased after a single sevuparin infusion and mature parasite IEs appeared transiently in the circulation. The effects observed on numbers of merozoites and throphozoites in the circulation, were detected already one hour after the first sevuparin injection. Here we report the development of a candidate drug named sevuparin that both blocks merozoite invasion and transiently de-sequesters IE in humans with P. falciparum malaria. Trial registration: ClinicalTrials.gov [ABSTRACT FROM AUTHOR]
- Published
- 2017
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- View/download PDF
28. Improved in vitro culture of plasmodium falciparum permits establishment of clinical isolates with preserved multiplication, invasion and rosetting phenotypes
- Author
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Ribacke, Ulf, Moll, Kirsten, Albrecht, Letusa, Ahmed Ismail, Hodan, Normark, Johan, Flaberg, Emilie, Szekely, Laszlo, Hultenby, Kjell, Persson, Kristina E. M., Egwang, Thomas G., Wahlgren, Mats, Ribacke, Ulf, Moll, Kirsten, Albrecht, Letusa, Ahmed Ismail, Hodan, Normark, Johan, Flaberg, Emilie, Szekely, Laszlo, Hultenby, Kjell, Persson, Kristina E. M., Egwang, Thomas G., and Wahlgren, Mats
- Abstract
To be able to robustly propagate P. falciparum at optimal conditions in vitro is of fundamental importance for genotypic and phenotypic studies of both established and fresh clinical isolates. Cryo-preserved P. falciparum isolates from Ugandan children with severe or uncomplicated malaria were investigated for parasite phenotypes under different in vitro growth conditions or studied directly from the peripheral blood. The parasite cultures showed a minimal loss of parasite-mass and preserved percentage of multiple infected pRBCs to that in peripheral blood, maintained adhesive phenotypes and good outgrowth and multiplication rates when grown in suspension and supplemented with gas. In contrast, abnormal and greatly fluctuating levels of multiple infections were observed during static growth conditions and outgrowth and multiplication rates were inferior. Serum, as compared to Albumax, was found necessary for optimal presentation of PfEMP1 at the pRBC surface and/or for binding of serum proteins (immunoglobulins). Optimal in vitro growth conditions of P. falciparum therefore include orbital shaking (50 rev/min), human serum (10%) and a fixed gas composition (5% O2, 5% CO2, 90% N2). We subsequently established 100% of 76 frozen patient isolates and found rosetting with schizont pRBCs in every isolate (>26% schizont rosetting rate). Rosetting during schizogony was often followed by invasion of the bound RBC as seen by regular and time-lapse microscopy as well as transmission electron microscopy. The peripheral parasitemia, the level of rosetting and the rate of multiplication correlated positively to one another for individual isolates. Rosetting was also more frequent with trophozoite and schizont pRBCs of children with severe versus uncomplicated malaria (p<0.002; p<0.004). The associations suggest that rosetting enhances the ability of the parasite to multiply within the human host.
- Published
- 2013
- Full Text
- View/download PDF
29. ABO Blood Group Antigen Decorated Giant Unilamellar Vesicles Exhibit Distinct Interactions with Plasmodium falciparumInfected Red Blood Cells
- Author
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Vagianou, Charikleia-Despoina, Stuhr-Hansen, Nicolai, Moll, Kirsten, Bovin, Nicolai, Wahlgren, Mats, and Blixt, Ola
- Abstract
Severe malaria is considered to be the deadliest disease of this century, primarily among children in sub-Saharan Africa. It stems from infection by the virulent parasite Plasmodium falciparum. The pathogenesis of the disease is based on the rosetting phenomenon, which occurs during the life cycle of the parasite in red blood cells (RBCs) and promotes the binding of parasitized RBCs to healthy ones. The role of the ABO blood group antigens in relation to the phenomenon has previously only been investigated in clinical isolates obtained from malaria patients. Here, we aim to clarify their role using synthetic ABO-decorated giant unilamellar vesicles (GUVs), which serve as simple biomimetic models of RBC-size cell membranes. Our results suggest clearly and for the first time that the blood group A and O antigens have a direct impact on receptor-specific rosetting phenomena when compared to the B antigen, which only participates in rosetting to an insignificant degree. Thus, glycodecorated GUVs represent a practical tool for studying cell-surface interactions.
- Published
- 2018
- Full Text
- View/download PDF
30. var gene transcription and PfEMP1 expression in the rosetting and cytoadhesive Plasmodium falciparum clone FCR3S1.2
- Author
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Albrecht, Letusa, Moll, Kirsten, Blomqvist, Karin, Normark, Johan, Chen, Qijun, Wahlgren, Mats, Albrecht, Letusa, Moll, Kirsten, Blomqvist, Karin, Normark, Johan, Chen, Qijun, and Wahlgren, Mats
- Abstract
Background: The pathogenicity of Plasmodium falciparum is in part due to the ability of the parasitized red blood cell (pRBC) to adhere to intra- vascular host cell receptors and serum-proteins. Binding of the pRBC is mediated by Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), a large multi-variant molecule encoded by a family of approximate to 60 var genes. Methods: The study of var gene transcription in the parasite clone FCR3S1.2 was performed by semi-quantitative PCR and quantitative PCR (qPCR). The expression of the major PfEMP1 in FCR3S1.2 pRBC was analysed with polyclonal sera in rosette disruption assays and immunofluorecence. Results: Transcripts from var1 (FCR3S1.2(var1); IT4var21) and other var genes were detected by semi-quantitative PCR but results from qPCR showed that one var gene transcript dominated over the others (FCR3S1.2var2; IT4var60). Antibodies raised in rats to the recombinant NTS-DBL1a of var2 produced in E. coli completely and dosedependently disrupted rosettes (approximate to 95% at a dilution of 1/5). The sera reacted with the Maurer's clefts in trophozoite stages (IFA) and to the infected erythrocyte surface (FACS) indicating that FCR3S1.2var2 encodes the dominant PfEMP1 expressed in this parasite. Conclusion: The major transcript in the rosetting model parasite FCR3S1.2 is FCR3S1.2var2 (IT4var60). The results suggest that this gene encodes the PfEMP1-species responsible for the rosetting phenotype of this parasite. The activity of previously raised antibodies to the NTS-DBL1a of FCR3S1.2var1 is likely due to cross-reactivity with NTS-DBL1 alpha of the var2 encoded PfEMP1.
- Published
- 2011
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31. Simultaneous transcription of duplicated var2csa gene copies in individual Plasmodium falciparum parasites
- Author
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Brolin, M, Ribacke, Ulf, Nilsson, Sandra, Ankarklev, Johan, Moll, Kirsten, Wahlgren, Mats, Chen, Qijun, Brolin, M, Ribacke, Ulf, Nilsson, Sandra, Ankarklev, Johan, Moll, Kirsten, Wahlgren, Mats, and Chen, Qijun
- Abstract
Background: Single nucleotide polymorphisms are common in duplicated genes, causing functional preservation, alteration or silencing. The Plasmodium falciparum genes var2csa and Pf332 are duplicated in the haploid genome of the HB3 parasite line. Whereas the molecular function of Pf332 remains to be elucidated, VAR2CSA is known to be the main adhesin in placental parasite sequestration. Sequence variations introduced upon duplication of these genes provide discriminative possibilities to analyze allele-specific transcription with a bearing towards understanding gene dosage impact on parasite biology. Results: We demonstrate an approach combining real-time PCR allelic discrimination and discriminative RNA-FISH to distinguish between highly similar gene copies in P. falciparum parasites. The duplicated var2csa variants are simultaneously transcribed, both on a population level and intriguingly also in individual cells, with nuclear co-localization of the active genes and corresponding transcripts. This indicates transcriptional functionality of duplicated genes, challenges the dogma of mutually exclusive var gene transcription and suggests mechanisms behind antigenic variation, at least in respect to the duplicated and highly similar var2csa genes. Conclusions: Allelic discrimination assays have traditionally been applied to study zygosity in diploid genomes. The assays presented here are instead successfully applied to the identification and evaluation of transcriptional activity of duplicated genes in the haploid genome of the P. falciparum parasite. Allelic discrimination and gene or transcript localization by FISH not only provide insights into transcriptional regulation of genes such as the virulence associated var genes, but also suggest that this sensitive and precise approach could be used for further investigation of genome dynamics and gene regulation.
- Published
- 2009
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- View/download PDF
32. A novel DBL-domain of the P. falciparum 332 molecule possibly involved in erythrocyte adhesion.
- Author
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Moll, Kirsten, Chêne, Arnaud, Ribacke, Ulf, Kaneko, Osamu, Nilsson, Sandra, Winter, Gerhard, Haeggström, Malin, Pan, Weiqing, Berzins, Klavs, Wahlgren, Mats, Chen, Qijun, Moll, Kirsten, Chêne, Arnaud, Ribacke, Ulf, Kaneko, Osamu, Nilsson, Sandra, Winter, Gerhard, Haeggström, Malin, Pan, Weiqing, Berzins, Klavs, Wahlgren, Mats, and Chen, Qijun
- Published
- 2007
33. Phagocytosis-inducing antibodies to Plasmodium falciparum upon immunization with a recombinant PfEMP1 NTS-DBL1α domain.
- Author
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Quintana, Maria del Pilar, Angeletti, Davide, Moll, Kirsten, Qijun Chen, and Wahlgren, Mats
- Subjects
PHAGOCYTOSIS ,IMMUNOGLOBULINS ,PLASMODIUM falciparum ,MALARIA immunology ,ERYTHROCYTES - Abstract
Background: Individuals living in endemic areas gradually acquire natural immunity to clinical malaria, largely dependent on antibodies against parasite antigens. There are many studies indicating that the variant antigen PfEMP1 at the surface of the parasitized red blood cell (pRBC) is one of the major targets of the immune response. It is believed that antibodies against PfEMP1 confer protection by blocking sequestration (rosetting and cytoadherence), inducing antibody-dependent cellular-inhibitory effect and opsonizing pRBCs for phagocytosis. Methods: A recombinant NTS-DBL1α domain from a rosette-mediating PfEMP1 was expressed in Escherichia coli. The resulting protein was purified and used for immunization to generate polyclonal (goat) and monoclonal (mouse) antibodies. The antibodies' ability to opsonize and induce phagocytosis in vitro was tested and contrasted with the presence of opsonizing antibodies naturally acquired during Plasmodium falciparum infection. Results: All antibodies recognized the recombinant antigen and the surface of live pRBCs, however, their capacity to opsonize the pRBCs for phagocytosis varied. The monoclonal antibodies isotyped as IgG2b did not induce phagocytosis, while those isotyped as IgG2a were in general very effective, inducing phagocytosis with similar levels as those naturally acquired during P. falciparum infection. These monoclonal antibodies displayed different patterns, some of them showing a concentration-dependent activity while others showed a prozone-like effect. The goat polyclonal antibodies were not able to induce phagocytosis. Conclusion: Immunization with an NTS-DBL1-α domain of PfEMP1 generates antibodies that not only have a biological role in rosette disruption but also effectively induce opsonization for phagocytosis of pRBCs with similar activity to naturally acquired antibodies from immune individuals living in a malaria endemic area. Some of the antibodies with high opsonizing activity were not able to disrupt rosettes, indicating that epitopes of the NTS-DBL1-α other than those involved in rosetting are exposed on the pRBC surface and are able to induce functional antibodies. The ability to induce phagocytosis largely depended on the antibody isotype and on the ability to recognize the surface of the pRBC regardless of the rosette-disrupting capacity. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
34. ARAM: an automated image analysis software to determine rosetting parameters and parasitaemia in Plasmodium samples.
- Author
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Kudella, Patrick Wolfgang, Moll, Kirsten, Wahlgren, Mats, Wixforth, Achim, and Westerhausen, Christoph
- Subjects
- *
PARASITEMIA , *PLASMODIUM , *ERYTHROCYTES , *MALARIA , *IMAGE analysis - Abstract
Background: Rosetting is associated with severe malaria and a primary cause of death in Plasmodium falciparum infections. Detailed understanding of this adhesive phenomenon may enable the development of new therapies interfering with rosette formation. For this, it is crucial to determine parameters such as rosetting and parasitaemia of laboratory strains or patient isolates, a bottleneck in malaria research due to the time consuming and error prone manual analysis of specimens. Here, the automated, free, stand-alone analysis software automated rosetting analyzer for micrographs (ARAM) to determine rosetting rate, rosette size distribution as well as parasitaemia with a convenient graphical user interface is presented. Methods: Automated rosetting analyzer for micrographs is an executable with two operation modes for automated identification of objects on images. The default mode detects red blood cells and fluorescently labelled parasitized red blood cells by combining an intensity-gradient with a threshold filter. The second mode determines object location and size distribution from a single contrast method. The obtained results are compared with standardized manual analysis. Automated rosetting analyzer for micrographs calculates statistical confidence probabilities for rosetting rate and parasitaemia. Results: Automated rosetting analyzer for micrographs analyses 25 cell objects per second reliably delivering identical results compared to manual analysis. For the first time rosette size distribution is determined in a precise and quantitative manner employing ARAM in combination with established inhibition tests. Additionally ARAM measures the essential observables parasitaemia, rosetting rate and size as well as location of all detected objects and provides confidence intervals for the determined observables. No other existing software solution offers this range of function. The second, non-malaria specific, analysis mode of ARAM offers the functionality to detect arbitrary objects. Conclusions: Automated rosetting analyzer for micrographs has the capability to push malaria research to a more quantitative and statistically significant level with increased reliability due to operator independence. As an installation file for Windows © 7, 8.1 and 10 is available for free, ARAM offers a novel open and easy-to-use platform for the malaria community to elucidate rosetting. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
35. Evasion of Immunity to Plasmodium falciparum: Rosettes of Blood Group A Impair Recognition of PfEMP1.
- Author
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Moll, Kirsten, Palmkvist, Mia, Ch'ng, Junhong, Kiwuwa, Mpungu Steven, and Wahlgren, Mats
- Subjects
- *
IMMUNITY , *PLASMODIUM falciparum , *ABO blood group system , *ERYTHROCYTES , *ENDOTHELIAL cells , *BLOOD platelets , *SERUM - Abstract
The ABO blood group antigens are expressed on erythrocytes but also on endothelial cells, platelets and serum proteins. Notably, the ABO blood group of a malaria patient determines the development of the disease given that blood group O reduces the probability to succumb in severe malaria, compared to individuals of groups A, B or AB. P. falciparum rosetting and sequestration are mediated by PfEMP1, RIFIN and STEVOR, expressed at the surface of the parasitized red blood cell (pRBC). Antibodies to these antigens consequently modify the course of a malaria infection by preventing sequestration and promoting phagocytosis of pRBC. Here we have studied rosetting P. falciparum and present evidence of an immune evasion mechanism not previously recognized. We find the accessibility of antibodies to PfEMP1 at the surface of the pRBC to be reduced when P. falciparum forms rosettes in blood group A RBC, as compared to group O RBC. The pRBC surrounds itself with tightly bound normal RBC that makes PfEMP1 inaccessible to antibodies and clearance by the immune system. Accordingly, pRBC of in vitro cloned P. falciparum devoid of ABO blood group dependent rosetting were equally well detected by anti-PfEMP1 antibodies, independent of the blood group utilized for their propagation. The pathogenic mechanisms underlying the severe forms of malaria may in patients of blood group A depend on the ability of the parasite to mask PfEMP1 from antibody recognition, in so doing evading immune clearance. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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- View/download PDF
36. Release of sequestered malaria parasites upon injection of a glycosaminoglycan
- Author
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Vogt, Anna M., Pettersson, Fredrik, Moll, Kirsten, Jonsson, Cathrine, Normark, Johan, Ribacke, Ulf, Egwang, Thomas G., Ekre, Hans-Peter, Spillmann, Dorothe, Chen, Qijun, Wahlgren, Mats, Vogt, Anna M., Pettersson, Fredrik, Moll, Kirsten, Jonsson, Cathrine, Normark, Johan, Ribacke, Ulf, Egwang, Thomas G., Ekre, Hans-Peter, Spillmann, Dorothe, Chen, Qijun, and Wahlgren, Mats
- Abstract
Severe human malaria is attributable to an excessive sequestration of Plasmodium falciparum-infected and uninfected erythrocytes in vital organs. Strains of P. falciparum that form rosettes and employ heparan sulfate as a host receptor are associated with development of severe forms of malaria. Heparin, which is similar to heparan sulfate in that it is composed of the same building blocks, was previously used in the treatment of severe malaria, but it was discontinued due to the occurrence of serious side effects such as intracranial bleedings. Here we report to have depolymerized heparin by periodate treatment to generate novel glycans (dGAG) that lack anticoagulant-activity. The dGAGs disrupt rosettes, inhibit merozoite invasion of erythrocytes and endothelial binding of P. falciparum-infected erythrocytes in vitro, and reduce sequestration in in vivo models of severe malaria. An intravenous injection of dGAGs blocks up to 80% of infected erythrocytes from binding in the micro-vasculature of the rat and releases already sequestered parasites into circulation. P. falciparum-infected human erythrocytes that sequester in the non-human primate Macaca fascicularis were similarly found to be released in to the circulation upon a single injection of 500 mu g of dGAG. We suggest dGAGs to be promising candidates for adjunct therapy in severe malaria.
- Published
- 2006
- Full Text
- View/download PDF
37. B-Cell Epitopes in NTS-DBL1α of PfEMP1 Recognized by Human Antibodies in Rosetting Plasmodium falciparum.
- Author
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Albrecht, Letusa, Angeletti, Davide, Moll, Kirsten, Blomqvist, Karin, Valentini, Davide, D'Alexandri, Fabio Luiz, Maurer, Markus, and Wahlgren, Mats
- Subjects
B cells ,PLASMODIUM falciparum ,IMMUNOGLOBULINS ,PLASMODIUM ,ERYTHROCYTES ,BLOOD flow - Abstract
Plasmodium falciparum is the most lethal of the human malaria parasites. The virulence is associated with the capacity of the infected red blood cell (iRBC) to sequester inside the deep microvasculature where it may cause obstruction of the blood-flow when binding is excessive. Rosetting, the adherence of the iRBC to uninfected erythrocytes, has been found associated with severe malaria and found to be mediated by the NTS-DBL1α-domain of Plasmodium falciparum Erythrocyte Membrane Protein 1 (PfEMP1). Here we show that the reactivity of plasma of Cameroonian children with the surface of the FCR3S1.2-iRBC correlated with the capacity to disrupt rosettes and with the antibody reactivity with a recombinant PfEMP1 (NTS-DBL1α of IT4
var60 ) expressed by parasite FCR3S1.2. The plasma-reactivity in a microarray, consisting of 96 overlapping 15-mer long peptides covering the NTS-DBL1α domain from IT4var60 sequence, was compared with their capacity to disrupt rosettes and we identified five peptides where the reactivity were correlated. Three of the peptides were localized in subdomain-1 and 2. The other two peptide-sequences were localized in the NTS-domain and in subdomain-3. Further, principal component analysis and orthogonal partial least square analysis generated a model that supported these findings. In conclusion, human antibody reactivity with short linear-peptides of NTS-DBL1α of PfEMP1 suggests subdomains 1 and 2 to hold anti-rosetting epitopes recognized by anti-rosetting antibodies. The data suggest rosetting to be mediated by the variable areas of PfEMP1 but also to involve structurally relatively conserved areas of the molecule that may induce biologically active antibodies. [ABSTRACT FROM AUTHOR]- Published
- 2014
- Full Text
- View/download PDF
38. Label-free microfluidic enrichment of ring-stage Plasmodium falciparum-infected red blood cells using non-inertial hydrodynamic lift.
- Author
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Geislinger, Thomas M., Sherwin Chan, Moll, Kirsten, Wixforth, Achim, Wahlgren, Mats, and Franke, Thomas
- Abstract
Background: Understanding of malaria pathogenesis caused by Plasmodium falciparum has been greatly deepened since the introduction of in vitro culture system, but the lack of a method to enrich ring-stage parasites remains a technical challenge. Here, a novel way to enrich red blood cells containing parasites in the early ring stage is described and demonstrated. Methods: A simple, straight polydimethylsiloxane microchannel connected to two syringe pumps for sample injection and two height reservoirs for sample collection is used to enrich red blood cells containing parasites in the early ring stage (8-10 h p.i.). The separation is based on the non-inertial hydrodynamic lift effect, a repulsive cell-wall interaction that enables continuous and label-free separation with deformability as intrinsic marker. Results: The possibility to enrich red blood cells containing P. falciparum parasites at ring stage with a throughput of ~12,000 cells per hour and an average enrichment factor of 4.3 ± 0.5 is demonstrated. Conclusion: The method allows for the enrichment of red blood cells early after the invasion by P. falciparum parasites continuously and without any need to label the cells. The approach promises new possibilities to increase the sensitivity of downstream analyses like genomic- or diagnostic tests. The device can be produced as a cheap, disposable chip with mass production technologies and works without expensive peripheral equipment. This makes the approach interesting for the development of new devices for field use in resource poor settings and environments, e.g. with the aim to increase the sensitivity of microscope malaria diagnosis. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
39. Improved In Vitro Culture of Plasmodium falciparum Permits Establishment of Clinical Isolates with Preserved Multiplication, Invasion and Rosetting Phenotypes.
- Author
-
Ribacke, Ulf, Moll, Kirsten, Albrecht, Letusa, Ahmed Ismail, Hodan, Normark, Johan, Flaberg, Emilie, Szekely, Laszlo, Hultenby, Kjell, Persson, Kristina E. M., Egwang, Thomas G., and Wahlgren, Mats
- Subjects
- *
PLASMODIUM falciparum , *PHENOTYPES , *CRYOPRESERVATION of organs, tissues, etc. , *MALARIA , *UGANDANS , *JUVENILE diseases , *IMMUNOGLOBULINS , *DISEASES - Abstract
To be able to robustly propagate P. falciparum at optimal conditions in vitro is of fundamental importance for genotypic and phenotypic studies of both established and fresh clinical isolates. Cryo-preserved P. falciparum isolates from Ugandan children with severe or uncomplicated malaria were investigated for parasite phenotypes under different in vitro growth conditions or studied directly from the peripheral blood. The parasite cultures showed a minimal loss of parasite-mass and preserved percentage of multiple infected pRBCs to that in peripheral blood, maintained adhesive phenotypes and good outgrowth and multiplication rates when grown in suspension and supplemented with gas. In contrast, abnormal and greatly fluctuating levels of multiple infections were observed during static growth conditions and outgrowth and multiplication rates were inferior. Serum, as compared to Albumax, was found necessary for optimal presentation of PfEMP1 at the pRBC surface and/or for binding of serum proteins (immunoglobulins). Optimal in vitro growth conditions of P. falciparum therefore include orbital shaking (50 rev/min), human serum (10%) and a fixed gas composition (5% O2, 5% CO2, 90% N2). We subsequently established 100% of 76 frozen patient isolates and found rosetting with schizont pRBCs in every isolate (>26% schizont rosetting rate). Rosetting during schizogony was often followed by invasion of the bound RBC as seen by regular and time-lapse microscopy as well as transmission electron microscopy. The peripheral parasitemia, the level of rosetting and the rate of multiplication correlated positively to one another for individual isolates. Rosetting was also more frequent with trophozoite and schizont pRBCs of children with severe versus uncomplicated malaria (p<0.002; p<0.004). The associations suggest that rosetting enhances the ability of the parasite to multiply within the human host. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
40. Analysis of antibody induction upon immunization with distinct NTS-DBL1a-domains of PfEMP1 from rosetting Plasmodium falciparum parasites.
- Author
-
Angeletti, Davide, Albrecht, Letusa, Wahlgren, Mats, and Moll, Kirsten
- Subjects
MALARIA prevention ,IMMUNOGLOBULINS ,IMMUNIZATION ,PLASMODIUM falciparum ,MALARIA vaccines ,EPITOPES ,PROTEIN microarrays - Abstract
Background: Rosette-formation of Plasmodium falciparum parasitized erythrocytes is of importance in the development of severe malaria. The parasite-derived molecule PfEMP1 (Plasmodium falciparum erythrocyte membrane protein 1), central to rosetting, is suggested to be included in a multimeric vaccine targeting severe disease. Methods: Three recombinant NTS-DBL1a-domains of PfEMP1 were generated in Escherichia coli, purified and used for immunization of rats and goats. Antibody titres were determined in ELISA assays and responses were compared in-between different individual animals and species. Reactivity with the parasites was tested in live pRBC using FACS. B-cell epitopes prediction was carried out in silico and compared to the results obtained by peptide microarray. Screening for serological cross-reactivity with heterologous NTS-DBL1a variants was carried out by ELISA, peptide array and FACS on pRBC of different laboratory strains and patient isolates. Results: All three NTS-DBL1a-domains induced high titres of antibodies that were biologically active with no apparent difference between constructs covering slightly different parts of the DBL1a-sequence. The different animal species showed comparable titres of antibodies, while variations within individuals of the species could be observed. Mapping of the recognized epitopes revealed that most parts of the molecule were able to induce an antibody response with a tendency for the N and C terminal parts of the molecule for slightly higher recognition. Important differences to the epitopes predicted were found as some of the most conserved parts of the DBL1a-domain contained the main epitopes for antibody reactivity. ELISA assays and peptide microarray demonstrated substantial cross-reactivity to heterologous variants, while binding to native PfEMP1 was observed only in few combinations on the pRBC surface, underlining that mainly internal, conserved and not surface exposed parts of the DBL1a-domain are responsible for this observation. Conclusion: Biologically active antibodies can be induced consistently, with high titres, in different animal species and the antibodies elicited by different constructs react with similar epitopes. Induced antibodies recognize epitopes localized in all subdomains of the DBL1a-sequence. Cross-reactivity between NTS-DBL1a-variants is common in ELISA, but rare with live pRBC emphasizing that also internal, conserved areas of PfEMP1 carry important highly immunogenic epitopes of the molecule [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
41. A Sequence in Subdomain 2 of DBL1α of Plasmodium falciparum Erythrocyte Membrane Protein 1 Induces Strain Transcending Antibodies.
- Author
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Blomqvist, Karin, Albrecht, Letusa, Quintana, Maria del Pilar, Angeletti, Davide, Joannin, Nicolas, Chêne, Arnaud, Moll, Kirsten, and Wahlgren, Mats
- Subjects
IMMUNITY ,MALARIA ,PLASMODIUM falciparum ,IMMUNOGLOBULINS ,ANTIGENS ,ERYTHROCYTE membranes - Abstract
Immunity to severe malaria is the first level of immunity acquired to Plasmodium falciparum. Antibodies to the variant antigen PfEMP1 (P. falciparum erythrocyte membrane protein 1) present at the surface of the parasitized red blood cell (pRBC) confer protection by blocking microvascular sequestration. Here we have generated antibodies to peptide sequences of subdomain 2 of PfEMP1-DBL1α previously identified to be associated with severe or mild malaria. A set of sera generated to the amino acid sequence KLQTLTLHQVREYWWALNRKEVWKA, containing the motif ALNRKE, stained the live pRBC. 50% of parasites tested (7/14) were positive both in flow cytometry and immunofluorescence assays with live pRBCs including both laboratory strains and in vitro adapted clinical isolates. Antibodies that reacted selectively with the sequence REYWWALNRKEVWKA in a 15-mer peptide array of DBL1a-domains were also found to react with the pRBC surface. By utilizing a peptide array to map the binding properties of the elicited anti-DBL1α antibodies, the amino acids WxxNRx were found essential for antibody binding. Complementary experiments using 135 degenerate RDSM peptide sequences obtained from 93 Ugandan patient-isolates showed that antibody binding occurred when the amino acids WxLNRKE/D were present in the peptide. The data suggests that the ALNRKE sequence motif, associated with severe malaria, induces strain-transcending antibodies that react with the pRBC surface. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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42. Plasmodium falciparum Rosetting Epitopes Converge in the SD3-Loop of PfEMP1-DBL1α.
- Author
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Angeletti, Davide, Albrecht, Letusa, Blomqvist, Karin, Del Pilar Quintana, María, Akhter, Tahmina, Bächle, Susanna M., Sawyer, Alan, Sandalova, Tatyana, Achour, Adnane, Wahlgren, Mats, and Moll, Kirsten
- Subjects
PLASMODIUM falciparum ,MICROBIAL virulence ,PARASITES ,GENETIC polymorphisms ,IMMUNOGLOBULINS ,MALARIA - Abstract
The ability of Plasmodium falciparum parasitized RBC (pRBC) to form rosettes with normal RBC is linked to the virulence of the parasite and RBC polymorphisms that weaken rosetting confer protection against severe malaria. The adhesin PfEMP1 mediates the binding and specific antibodies prevent sequestration in the micro-vasculature, as seen in animal models. Here we demonstrate that epitopes targeted by rosette disrupting antibodies converge in the loop of subdomain 3 (SD3) which connects the h6 and h7 α-helices of PfEMP1-DBL1α. Both monoclonal antibodies and polyclonal IgG, that bound to epitopes in the SD3-loop, stained the surface of pRBC, disrupted rosettes and blocked direct binding of recombinant NTS-DBL1α to RBC. Depletion of polyclonal IgG raised to NTS-DBL1α on a SD3 loop-peptide removed the anti-rosetting activity. Immunizations with recombinant subdomain 1 (SD1), subdomain 2 (SD2) or SD3 all generated antibodies reacting with the pRBC-surface but only the sera of animals immunized with SD3 disrupted rosettes. SD3-sequences were found to segregate phylogenetically into two groups (A/B). Group A included rosetting sequences that were associated with two cysteineresidues present in the SD2-domain while group B included those with three or more cysteines. Our results suggest that the SD3 loop of PfEMP1-DBL1α is an important target of anti-rosetting activity, clarifying the molecular basis of the development of variant-specific rosette disrupting antibodies. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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43. Plasmodium falciparum Antigen 332 Is a Resident Peripheral Membrane Protein of Maurer's Clefts.
- Author
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Nilsson, Sandra, Angeletti, Davide, Wahlgren, Mats, Qijun Chen, and Moll, Kirsten
- Subjects
PLASMODIUM falciparum ,CYTOSOL ,CYTOSKELETON ,IMMUNOFLUORESCENCE ,CYTOMETRY ,PLASMODIUM - Abstract
During the intraerythrocytic development of Plasmodium falciparum, the malaria parasite remodels the host cell cytosol by inducing membranous structures termed Maurer's clefts and inserting parasite proteins into the red blood cell cytoskeleton and plasma membrane. Pf332 is the largest known asexual malaria antigen that is exported into the red blood cell cytosol where it associates with Maurer's clefts. In the current work, we have utilized a set of different biochemical assays to analyze the solubility of the endogenous Pf332 molecule during its trafficking from the endoplasmic reticulum within the parasite to the host cell cytosol. Solubilization studies demonstrate that Pf332 is synthesized and trafficked within the parasite as a peripheral membrane protein, which after export into the host cell cytosol associates with the cytoplasmic side of Maurer's clefts in a peripheral manner. By immunofluorescence microscopy and flow cytometry, we show that Pf332 persists in close association with Maurer's clefts throughout trophozoite maturation and schizogony, and does not become exposed at the host cell surface. Our data also indicate that Pf332 interacts with the host cell cytoskeleton, but only in very mature parasite stages. Thus, the present study describes Pf332 as a resident peripheral membrane protein of Maurer's clefts and suggests that the antigen participates in host cytoskeleton modifications at completion of the intraerythrocytic developmental cycle. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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44. Generation of Cross-Protective Antibodies against Plasmodium falciparum Sequestration by Immunization with an Erythrocyte Membrane Protein 1-Duffy Binding-Like 1 Domain
- Author
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Moll, Kirsten, Pettersson, Fredrik, Vogt, Anna M., Jonsson, Cathrine, Rasti, Niloofar, Ahuja, Sanjay, Spångberg, Mats, Mercereau-Puijalon, Odile, Arnot, David E., Wahlgren, Mats, and Chen, Qijun
- Abstract
The Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is an important virulence factor on the surface of infected erythrocytes. Naturally acquired antibodies to PfEMP1 expressed by parasites causing severe malaria are suggested to be protective and of major interest for the development of a vaccine against severe disease. In this study, the PfEMP1 expressed by a parasite clone displaying a multiadhesive phenotype associated with severe malaria was well recognized by sera of malaria semi-immune children. The efficiency of the Duffy binding-like 1 (DBL1) domain of this PfEMP1 was therefore, alone or in combination with two additional DBL1 domains, evaluated as a potential vaccine candidate using both a rodent model and a primate model. Antibodies against the DBL1 domain were generated by immunization with recombinant DBL1-Semliki Forest virus particles and recombinant protein and analyzed in vitro. The immunized animals were challenged in vivo with various parasite strains or clones. Immunization with the PfEMP1-DBL1 domain abolished the PfEMP1-dependent sequestration of the homologous strain in immunized rats and substantially inhibited parasite adhesion in immunized monkeys. Protection against sequestration of heterologous parasite strains was also confirmed by direct or indirect challenge in the rat model. These results strongly support the use of the DBL1 domain in the development of a vaccine targeting severe malaria.
- Published
- 2007
45. Generation of Cross-Protective Antibodies against Plasmodium falciparumSequestration by Immunization with an Erythrocyte Membrane Protein 1-Duffy Binding-Like 1α Domain
- Author
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Moll, Kirsten, Pettersson, Fredrik, Vogt, Anna M., Jonsson, Cathrine, Rasti, Niloofar, Ahuja, Sanjay, Spångberg, Mats, Mercereau-Puijalon, Odile, Arnot, David E., Wahlgren, Mats, and Chen, Qijun
- Abstract
ABSTRACTThe Plasmodium falciparumerythrocyte membrane protein 1 (PfEMP1) is an important virulence factor on the surface of infected erythrocytes. Naturally acquired antibodies to PfEMP1 expressed by parasites causing severe malaria are suggested to be protective and of major interest for the development of a vaccine against severe disease. In this study, the PfEMP1 expressed by a parasite clone displaying a multiadhesive phenotype associated with severe malaria was well recognized by sera of malaria semi-immune children. The efficiency of the Duffy binding-like 1α (DBL1α) domain of this PfEMP1 was therefore, alone or in combination with two additional DBL1α domains, evaluated as a potential vaccine candidate using both a rodent model and a primate model. Antibodies against the DBL1α domain were generated by immunization with recombinant DBL1α-Semliki Forest virus particles and recombinant protein and analyzed in vitro. The immunized animals were challenged in vivo with various parasite strains or clones. Immunization with the PfEMP1-DBL1α domain abolished the PfEMP1-dependent sequestration of the homologous strain in immunized rats and substantially inhibited parasite adhesion in immunized monkeys. Protection against sequestration of heterologous parasite strains was also confirmed by direct or indirect challenge in the rat model. These results strongly support the use of the DBL1α domain in the development of a vaccine targeting severe malaria.
- Published
- 2007
- Full Text
- View/download PDF
46. Rosette-Disrupting Effect of an Anti-Plasmodial Compound for the Potential Treatment of Plasmodium falciparum Malaria Complications.
- Author
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Ch'ng, Jun-Hong, Moll, Kirsten, Quintana, Maria del Pilar, Chan, Sherwin Chun Leung, Masters, Ellen, Moles, Ernest, Liu, Jianping, Eriksson, Anders B., and Wahlgren, Mats
- Published
- 2016
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47. EFFECT ON ROSETTE FORMATION OF ANTIBODIES TO DUFFY BINDING-LIKE 1 ALPHA DOMAIN OF PLASMODIUM FALCIPARUM ERYTHROCYTE MEMBRANE PROTEIN 1.
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Saiwaew, Somporn, Moll, Kirsten, Leitgeb, Anna M., Piaraksa, Nattaporn, Sila, Patima, Patthanacharoern, Napaporn, Phetsouvanh, Rattanaphone, Charunwatthana, Prakaykaew, Uthaisin, Chirapong, Dondorp, Arjen M., Wahlgren, Mats, and Chotivanich, Kesinee
- Published
- 2016
48. Correction: Evasion of Immunity to Plasmodium falciparum: Rosettes of Blood Group A Impair Recognition of PfEMP1.
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Moll, Kirsten, Palmkvist, Mia, Ch'ng, Junhong, Kiwuwa, Mpungu Steven, and Wahlgren, Mats
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- *
PUBLISHED errata , *BIOLOGICAL periodicals , *PERIODICAL publishing , *PERIODICAL articles , *PUBLISHING , *PUBLISHED articles , *PUBLICATIONS - Published
- 2016
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49. Simultaneous transcription of duplicated var2csa gene copies in individual Plasmodium falciparum parasites
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Brolin, Kim, Ribacke, Ulf, Nilsson, Sandra, Ankarklev, Johan, Moll, Kirsten, Wahlgren, Mats, and Chen, Qijun
- Abstract
Single nucleotide polymorphisms are common in duplicated genes, causing functional preservation, alteration or silencing. The Plasmodium falciparum genes var2csa and Pf332 are duplicated in the haploid genome of the HB3 parasite line. Whereas the molecular function of Pf332 remains to be elucidated, VAR2CSA is known to be the main adhesin in placental parasite sequestration. Sequence variations introduced upon duplication of these genes provide discriminative possibilities to analyze allele-specific transcription with a bearing towards understanding gene dosage impact on parasite biology.
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- 2009
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50. Antibiotic biocompatibility assay and anti-biofilm strategies for Pseudomonas aeruginosa infection in bioengineered artificial skin substitutes.
- Author
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Quiñones-Vico MI, Andrades-Amate M, Fernández-González A, Ubago-Rodríguez A, Moll K, Norrby-Teglund A, Svensson M, Gutiérrez-Fernández J, and Arias-Santiago S
- Abstract
Objectives: Bioengineered artificial skin substitutes (BASS) are an advanced therapy for treating extensively burned patients. Pseudomonas aeruginosa (P. aeruginosa) infections represent a major challenge in these patients as formation of biofilms impede wound healing and perpetuate a chronic inflammatory state. Here we assessed antibiotics (alone or in combination) with respect to cytotoxicity, as well as antimicrobial efficacy in P. aeruginosa biofilm formed on infection of BASS., Methods: Cell viability, structure and functionality were evaluated using microscopy and trans-epidermal water loss analyses, respectively. BASS were established and infected for 24 h to allow P. aeruginosa biofilm formation, after which two antimicrobial approaches, treatment and prevention, were tested. In the latter, antibiotics were added to BASS before infection. The antimicrobial effect was determined using real-time calorimetry., Results: In dose-response experiments, 1.25 mg/mL amikacin, 0.02 mg/mL ciprofloxacin, 0.051 mg/mL colistin, 1 mg/mL meropenem and colistin in combination with either amikacin, ciprofloxacin and meropenem did not affect BASS' viability, structure and functionality. All antibiotics, except colistin, showed effective antimicrobial activity at these non-cytotoxic concentrations. For concentrations below the highest non-cytotoxic ones, successive treatments resulted in higher bacterial metabolic rates. Only the combinations managed to eradicate the infection with repeated treatments. With respect to prevention of infection, all antibiotics at the highest non-cytotoxic concentrations and the combinations were effective. This preventive capacity was maintained for at least 5 days., Conclusion: The findings highlight the potential for developing BASS with antimicrobial properties that can prevent infections during wound healing in burn patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
- Published
- 2024
- Full Text
- View/download PDF
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