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Exposure to Plasmodium falciparum-derived hemozoin leads to impairment of transcriptional activation upon dendritic cell maturation
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
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(English)Manuscript (preprint) (Other academic)
National Category
Immunology
Research subject
Immunology
Identifiers
URN: urn:nbn:se:su:diva-125623OAI: oai:DiVA.org:su-125623DiVA: diva2:894567
Available from: 2016-01-15 Created: 2016-01-15 Last updated: 2016-01-25Bibliographically approved
In thesis
1. Plasmodium falciparum-mediated modulation of innate immune cells: responses and regulation
Open this publication in new window or tab >>Plasmodium falciparum-mediated modulation of innate immune cells: responses and regulation
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Plasmodium falciparum (P. falciparum) infection modulates the response of innate immune cells. The aim of this work was to study the impact of P. falciparum infection and P. falciparum-derived molecules on the response of dendritic cells (DC) and monocytes.

In paper I we investigated the effects of natural hemozoin (nHZ), a P. falciparum-derived molecule, on the phenotype and functionality of DC. We found that exposure to nHZ impaired the capacity of DC to mature. Paper II is a follow-up on paper I, where the underlying transcriptional events preceding the nHZ-induced impairment of DC maturation were investigated. More specifically, we examined the involvement of certain transcription factors, subunits of chromatin remodeling complexes and histone modifications in the regulation of DC maturation. Our findings suggest that nHZ-exposure of DC does not lead to recruitment or enrichment of molecules needed for transcriptional activation. In paper III we investigated P. falciparum effects in vivo in sympatric ethnic groups with differential susceptibility towards P. falciparum infection living in Burkina Faso. The aim of this study was to establish the transcriptional networks underlying the relatively better protection against P. falciparum infection observed in the Fulani ethnic group compared to other sympatric ethnic groups. Our findings reveal differential gene expression in monocytes of infected Fulani compared to uninfected Fulani and the difference concerned multiple classes of genes including signal transduction, immunological responses and chromatin remodelers. The results provide new aspects on molecules and regulatory mechanisms that are involved in the relatively more protective response against P. falciparum infection.

Taken together, the work presented in this thesis leads to a deeper understanding of the P. falciparum-induced modulation of responses of innate immune cells and the underlying mechanisms possibly regulating those responses.

Place, publisher, year, edition, pages
Stockholm: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 2016. 56 p.
Keyword
Plasmodium falciparum, hemozoin, innate immune cells, sympatric ethnic groups
National Category
Biological Sciences
Research subject
Immunology
Identifiers
urn:nbn:se:su:diva-126138 (URN)978-91-7649-296-3 (ISBN)
Public defence
2016-03-17, Vivi Täckholmsalen (Q-salen), NPQ-huset, Svante Arrheniusväg 20 A, Stockholm, 09:30 (English)
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Note

At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 2: Manuscript. Paper 3: Manuscript.

Available from: 2016-02-23 Created: 2016-01-25 Last updated: 2016-02-15Bibliographically approved

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Bujila, IoanaTroye-Blomberg, MaritaÖstlund Farrants, Ann-Kristin
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