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Studies on malaria blood stage infection and host responses
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The challenges in controlling malaria infectious disease are increasing due to drug resistance and incomplete immunity induced by malaria infection. Moreover there is no effective vaccine available against malaria blood stage infection. Fortunately the completions of the genomic sequences of several Plasmodium species and their bioinformatic analyses have revealed gene homologies indicating the considerable homologies between the human parasite P. falciparum and the mouse parasite P. yoelii. We investigated intensively the presence of functionally and antigenically conserved domains between P. falciparum and P. yoelii at asexual blood-stages. We took advantage of P. yoelii infection to study malaria anemia in a mouse malaria model that focused on cytokines and the cells producing them. Moreover, we explored antibodies reactive with the intraerythrocytic parasite antigen Pf332 for their effect on parasite growth in vitro in cooperation with human monocytes. Taken together, the whole study unlocks a few windows of malaria infection in host responses and we may need to change our strategies in fighting against malaria parasites by enlarging our scope of choosing components as vaccine candidates to control the disease. 

Place, publisher, year, edition, pages
Stockholm: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University , 2013. , 80 p.
Keyword [en]
Malaria, cytokines, parasite ligands, merozoite released soluble proteins (MRSPs)
National Category
Immunology
Research subject
Molecular Biosciences
Identifiers
URN: urn:nbn:se:su:diva-93732ISBN: 978-91-7447-761-0 (print)OAI: oai:DiVA.org:su-93732DiVA: diva2:648210
Public defence
2013-10-10, Ahlmannsalen, Geovetenskapens hus, Svante Arrhenius väg 12, Stockholm, 10:00 (English)
Opponent
Supervisors
Projects
Malaria, cytokines, parasite ligands, merozoite released soluble proteins (MRSPs)
Note

At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 3: Manuscript.

Available from: 2013-09-18 Created: 2013-09-13 Last updated: 2013-09-19Bibliographically approved
List of papers
1. Plasmodium yoelii: experimental evidences for the conserved epitopes between mouse and human malaria parasite, Plasmodium falciparum.
Open this publication in new window or tab >>Plasmodium yoelii: experimental evidences for the conserved epitopes between mouse and human malaria parasite, Plasmodium falciparum.
2007 (English)In: Exp Parasitol, ISSN 0014-4894, Vol. 116, no 3, 214-24 p.Article in journal (Refereed) Published
Keyword
Animals, Antibodies; Protozoan/immunology, Antigens; Protozoan/chemistry/*immunology, Conserved Sequence/immunology, Cross Reactions, Electrophoresis; Polyacrylamide Gel, Epitopes/chemistry/*immunology, Erythrocytes/immunology/parasitology, Fluorescent Antibody Technique, Humans, Immunoprecipitation, Malaria/prevention & control, Malaria Vaccines, Male, Merozoites/immunology, Mice, Mice; Inbred C57BL, Plasmodium falciparum/*immunology, Plasmodium yoelii/*immunology, Specific Pathogen-Free Organisms
Identifiers
urn:nbn:se:su:diva-19720 (URN)000247662500004 ()17336297 (PubMedID)
Available from: 2008-01-18 Created: 2008-01-18 Last updated: 2013-09-16Bibliographically approved
2. Cytokine dysregulation associated with malarial anemia in Plasmodium yoelii infected mice
Open this publication in new window or tab >>Cytokine dysregulation associated with malarial anemia in Plasmodium yoelii infected mice
2013 (English)In: American Journal of Translational Research, ISSN 1943-8141, E-ISSN 1943-8141, Vol. 5, no 2, 235-245 p.Article in journal (Refereed) Published
Abstract [en]

The mechanisms of malaria anemia remain incompletely understood although much effort has been put on studies in both human and murine systems. Hematopoiesis is regulated by the proliferation, differentiation and maturation of erythropoietic progenitor cells into erythrocytes and is tightly controlled by a complex communication network of cytokines as signal mediators. The present study used the murine P. yoelii 17XNL malaria model to investigate the profile of cytokines and leukocytes throughout the entire infection. Moreover, malaria induced anemia was studied in comparison with anemia induced by hemorrhage and hemolysis. During the P. yoelii infection, the levels of erythropoietic-related cytokines, such as G-CSF, GMCSF, IL-7, and IL-17, were pronouncedly reduced, while those of regulatory cytokines, such as IL-10 and TNF-alpha, were constantly increased. This cytokine profile corresponded well with the cellular composition during the infection, such as drastically decreased levels of CD4(+) and CD8(+) T cells. The profiles of erythropoiesis or hematopoiesis related cytokines during malarial anemia showed striking differences from those during anemia induced by hemorrhage or hemolysis. This study demonstrates that a markedly dysregulated cytokine network occurred in this murine malaria model, which may open a new window of insight into the mechanisms of malaria related anemia.

Keyword
Malaria, Plasmodium yoelii, anemia, hematopoiesis, IL-7, IL-17, Epo, cytokine
National Category
Cancer and Oncology Medical Biotechnology
Identifiers
urn:nbn:se:su:diva-90808 (URN)000318281300011 ()
Funder
NIH (National Institute of Health), 5 P50 HL 54459-09Swedish Research Council
Note

AuthorCount:4;

Available from: 2013-06-12 Created: 2013-06-11 Last updated: 2017-12-06Bibliographically approved
3. Antibodies to the Plasmodiumfalciparum antigen Pf332 cooperated with human monocytes inhibit parasitegrowth by inducing intraerythrocytic abnormal parasite forms in vitro
Open this publication in new window or tab >>Antibodies to the Plasmodiumfalciparum antigen Pf332 cooperated with human monocytes inhibit parasitegrowth by inducing intraerythrocytic abnormal parasite forms in vitro
Show others...
(English)Manuscript (preprint) (Other academic)
Abstract [en]

IntraerythrocyticPlasmodium parasite proliferation istightly related to disease seriousness. Intraerythrocytic parasite developmentis fundamental to the proliferation of the malaria parasite which is affectedby many factors. Antibodies inhibiting intraerythrocytic parasite growth ordevelopment have been long indicated in protective immune mechanisms,particularly in cooperation with human monocytes. Here, we show that the developmentP. falciparum intraerythrocyticparasite was significantly disturbed by antibodies reactive with theintraerythrocytic parasitic antigen Pf332 by inducing parasites with anabnormal morphology. A synergistic effect in the induction of the abnormal formswas seen when antibodies cooperated with human monocytes. The long period of 48hours intraerythrocytic development provides a greater opportunity for antibodiesto react with the intraerythrocytic antigens than with merozoite stage antigens,which are exposed only for a short period of time.

National Category
Immunology
Identifiers
urn:nbn:se:su:diva-93781 (URN)
Available from: 2013-09-16 Created: 2013-09-16 Last updated: 2013-09-16Bibliographically approved

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