Abstract
Schistosomes are parasitic worms that cause schistosomiasis, a chronic disease associated
with a Th2 response. During the chronic phase of infection the disease is also associated
with enhanced IL-10 production and suppressed T cell proliferation against parasite and
third party antigens. The tegumental outer-surface structure of schistosomes is unique in
nature and consists of a syncytium of fused cells covered by two closely-apposed lipid
bilayers that form the interactive surface with the host. Schistosome-specific
lysophosphatidylserine (lysoGPSer) activates toll-like receptor 2 (TLR2) and affects
dendritic cells in such a way that mature dendritic cells gain the ability to induce the
development of IL-10 producing regulatory T cells.
We present a novel HPLC-MS/MS method that separates molecular species of all
phospholipid classes in one single run. Using this method, more that 400 phospholipid
species were identified and quantified in crude lipid extracts from Schistosoma mansoni.
Furthermore, we analysed the phospholipid species composition of phosphatidylserine
and lysophospholipids in adult worms, in isolated tegumental membranes of adult
schistosomes and in blood cells of the host. It was shown that the tegument comprises
many schistosome-specific and tegument-specific phospholipids. We also show that
lysophosphatidylserine species with saturated acyl chains containing 16 to 20 carbon
atoms have very poor activating capacity, while long chain lysophosphatidyl species (22
carbon atoms of longer) have a potent TLR2 activating capacity. Finally, we show the
effect of schistosomal lipid fractions on the immune system of Gabonese children living
in an area endemic for schistosomiasis. A lipid fraction contained lysophospahtidylserine
(lysoGPSer) plus diacylphosphatidylserine (GPSer) while the other one contained
lysoGPSer and only a trace of GPSer. The effect of the lipid fractions was compared with
commercial available TLR2 ligands. LysoGPSer plus GPSer was shown to have different
immunological effects compared to lysoGPser.
with a Th2 response. During the chronic phase of infection the disease is also associated
with enhanced IL-10 production and suppressed T cell proliferation against parasite and
third party antigens. The tegumental outer-surface structure of schistosomes is unique in
nature and consists of a syncytium of fused cells covered by two closely-apposed lipid
bilayers that form the interactive surface with the host. Schistosome-specific
lysophosphatidylserine (lysoGPSer) activates toll-like receptor 2 (TLR2) and affects
dendritic cells in such a way that mature dendritic cells gain the ability to induce the
development of IL-10 producing regulatory T cells.
We present a novel HPLC-MS/MS method that separates molecular species of all
phospholipid classes in one single run. Using this method, more that 400 phospholipid
species were identified and quantified in crude lipid extracts from Schistosoma mansoni.
Furthermore, we analysed the phospholipid species composition of phosphatidylserine
and lysophospholipids in adult worms, in isolated tegumental membranes of adult
schistosomes and in blood cells of the host. It was shown that the tegument comprises
many schistosome-specific and tegument-specific phospholipids. We also show that
lysophosphatidylserine species with saturated acyl chains containing 16 to 20 carbon
atoms have very poor activating capacity, while long chain lysophosphatidyl species (22
carbon atoms of longer) have a potent TLR2 activating capacity. Finally, we show the
effect of schistosomal lipid fractions on the immune system of Gabonese children living
in an area endemic for schistosomiasis. A lipid fraction contained lysophospahtidylserine
(lysoGPSer) plus diacylphosphatidylserine (GPSer) while the other one contained
lysoGPSer and only a trace of GPSer. The effect of the lipid fractions was compared with
commercial available TLR2 ligands. LysoGPSer plus GPSer was shown to have different
immunological effects compared to lysoGPser.
| Original language | English |
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| Qualification | Doctor of Philosophy |
| Awarding Institution |
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| Supervisors/Advisors |
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| Award date | 2 Jul 2007 |
| Place of Publication | Utrecht |
| Print ISBNs | 978-90-393-4571-9 |
| Publication status | Published - 2 Jul 2007 |