Abstract
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Malaria Journal |
| Vol/bind | 4 |
| Udgave nummer | 1 |
| Sider (fra-til) | 21 |
| ISSN | 1475-2875 |
| DOI | |
| Status | Udgivet - 2005 |
Bibliografisk note
Keywords: Animals; Antigens, Surface; Blotting, Western; Cell Line; Flow Cytometry; Gene Expression; Gene Expression Profiling; Humans; Immunoglobulin G; Malaria, Falciparum; Parasitemia; Plasmodium falciparum; Polymerase Chain Reaction; Protozoan Proteins; Reproduction, Asexual; Time Factors; Transcription, GeneticAdgang til dokumentet
Citationsformater
- APA
- Standard
- Harvard
- Vancouver
- Author
- BIBTEX
- RIS
Expression of Plasmodium falciparum erythrocyte membrane protein 1 in experimentally infected humans. / Lavstsen, Thomas; Magistrado, Pamela; Hermsen, Cornelus C; Salanti, Ali; Jensen, Anja T R; Sauerwein, Robert; Hviid, Lars; Theander, Thor G; Staalsoe, Trine.
I: Malaria Journal, Bind 4, Nr. 1, 2005, s. 21.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
}
TY - JOUR
T1 - Expression of Plasmodium falciparum erythrocyte membrane protein 1 in experimentally infected humans
AU - Lavstsen, Thomas
AU - Magistrado, Pamela
AU - Hermsen, Cornelus C
AU - Salanti, Ali
AU - Jensen, Anja T R
AU - Sauerwein, Robert
AU - Hviid, Lars
AU - Theander, Thor G
AU - Staalsoe, Trine
N1 - Keywords: Animals; Antigens, Surface; Blotting, Western; Cell Line; Flow Cytometry; Gene Expression; Gene Expression Profiling; Humans; Immunoglobulin G; Malaria, Falciparum; Parasitemia; Plasmodium falciparum; Polymerase Chain Reaction; Protozoan Proteins; Reproduction, Asexual; Time Factors; Transcription, Genetic
PY - 2005
Y1 - 2005
N2 - BACKGROUND: Parasites causing severe malaria in non-immune patients express a restricted subset of variant surface antigens (VSA), which are better recognized by immune sera than VSA expressed during non-severe disease in semi-immune individuals. The most prominent VSA are the var gene-encoded Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family, which is expressed on the surface of infected erythrocytes where it mediates binding to endothelial receptors. Thus, severe malaria may be caused by parasites expressing PfEMP1 variants that afford parasites optimal sequestration in immunologically naive individuals and high effective multiplication rates. METHODS: var gene transcription was analysed using real time PCR and PfEMP1 expression by western blots as well as immune plasma recognition of parasite cultures established from non-immune volunteers shortly after infection with NF54 sporozoites. RESULTS: In cultures representing the first generation of parasites after hepatic release, all var genes were transcribed, but Group A var genes were transcribed at the lowest levels. In cultures established from second or third generation blood stage parasites of volunteers with high in vivo parasite multiplication rates, the var gene transcription pattern differed markedly from the transcription pattern of the cultures representing first generation parasites. This indicated that parasites expressing specific var genes, mainly belonging to group A and B, had expanded more effectively in vivo compared to parasites expressing other var genes. The differential expression of PfEMP1 was confirmed at the protein level by immunoblot analysis. In addition, serological typing showed that immune sera more often recognized second and third generation parasites than first generation parasites. CONCLUSION: In conclusion, the results presented here support the hypothesis that parasites causing severe malaria express a subset of PfEMP1, which bestows high parasite growth rates in individuals with limited pre-existing immunity.
AB - BACKGROUND: Parasites causing severe malaria in non-immune patients express a restricted subset of variant surface antigens (VSA), which are better recognized by immune sera than VSA expressed during non-severe disease in semi-immune individuals. The most prominent VSA are the var gene-encoded Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family, which is expressed on the surface of infected erythrocytes where it mediates binding to endothelial receptors. Thus, severe malaria may be caused by parasites expressing PfEMP1 variants that afford parasites optimal sequestration in immunologically naive individuals and high effective multiplication rates. METHODS: var gene transcription was analysed using real time PCR and PfEMP1 expression by western blots as well as immune plasma recognition of parasite cultures established from non-immune volunteers shortly after infection with NF54 sporozoites. RESULTS: In cultures representing the first generation of parasites after hepatic release, all var genes were transcribed, but Group A var genes were transcribed at the lowest levels. In cultures established from second or third generation blood stage parasites of volunteers with high in vivo parasite multiplication rates, the var gene transcription pattern differed markedly from the transcription pattern of the cultures representing first generation parasites. This indicated that parasites expressing specific var genes, mainly belonging to group A and B, had expanded more effectively in vivo compared to parasites expressing other var genes. The differential expression of PfEMP1 was confirmed at the protein level by immunoblot analysis. In addition, serological typing showed that immune sera more often recognized second and third generation parasites than first generation parasites. CONCLUSION: In conclusion, the results presented here support the hypothesis that parasites causing severe malaria express a subset of PfEMP1, which bestows high parasite growth rates in individuals with limited pre-existing immunity.
U2 - 10.1186/1475-2875-4-21
DO - 10.1186/1475-2875-4-21
M3 - Journal article
C2 - 15857512
VL - 4
SP - 21
JO - Malaria Journal
JF - Malaria Journal
SN - 1475-2875
IS - 1
ER -