Carbohydrate-mediated adhesion in Plasmodium falciparum malaria
Notice bibliographique
Résumé
Characterization of virulence factors in P. falciparum malaria is essential in order to identify new therapeutic and prophylactic targets. Rosette formation, the binding of uninfected red blood cells to parasite-infected red blood cells, is a P. falciparum virulence phenotype associated with severe clinical manifestations, e. g. cerebral malaria and severe anemia. Humoral responses to rosetting epitopes seem to confer protective immunity and we have shown in these studies that individuals living in malaria endemic areas build up age-related humoral responses to rosetting epitopes that parallel the development of clinical immunity. Furthermore, epitopes that mediate the rosetting phenotype appear to be diverse but conserved between distant regions in Africa. We have performed a detailed study of the cell-cell binding mechanisms that govern rosetting. Polysaccharides belonging to the glycosaminoglycan family, especially heparin and heparan sulfate, inhibit rosette formation and treatments of host cells indicate that heparan sulfate-like glycans support adhesion. In addition, the ABO blood group phenotype of the infected host modulates rosetting and blood group A and B antigens have been shown to function as co-receptors to other receptors in rosetting. The parasite-derived adhesion molecule that mediates rosetting has been identified as a Plasmodium falciparum erythrocyte membrane protein I (PfEMP1) variant, a product of the vast family of var genes. PfEMP1 mediates adhesion by interacting with host cell glycan receptors, such as heparan sulfate and blood group A antigen. We have characterized the binding of heparan sulfate and heparin to the rosetting domain of PfEMP1. Important molecular features of oligosaccharides required for optimal binding, such as molecular size (12-mer oligosaccharide chain or larger) and N-sulfation, have thus been identified. In field studies, the heparin-binding phenotype of P. falciparum was found to be more common among patients with severe malaria. Furthermore, the clinical isolates had the ability to adhere to multiple receptors. We have characterized the binding properties of PfEMP1. to multiple host receptors, which may explain the poly-adhesive P. falciparum phenotype associated with severe disease in these studies. The present investigation contributes to the molecular elucidation of virulent adhesive phenotypes in P. falciparum malaria. The identified molecules involved in the cell-cell adherence may serve as targets for prophylactic and therapeutic measures. List of scientific papers I. Barragan A, Kremsner PG, Weiss W, Wahlgren M, Carlson J (1998). Age-related buildup of humoral immunity against epitopes for rosette formation and agglutination in African areas of malaria endemicity. Infect Immun. 66(10):4783-4787. https://pubmed.ncbi.nlm.nih.gov/9746579 II. Chen Q, Barragan A, Fernandez V, Sundström A, Schlichtherle M, Sahlén A, Carlson J, Datta S, Wahlgren M (1998). Identification of Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) as the rosetting ligand of the malaria parasite P. falciparum. J Exp Med. 187(1):15-23. https://pubmed.ncbi.nlm.nih.gov/9419207 III. Barragan A, Spillmann D, Kremsner PG, Wahlgren M, Carlson J (1999). Plasmodium falciparum: molecular background to strain-specific rosette disruption by glycosaminoglycans and sulfated glycoconjugates. Exp Parasitol. 91(2):133-143. https://pubmed.ncbi.nlm.nih.gov/9990341 IV. Barragan A, Fernandez V, Chen Q, von Euler A, Wahlgren M, Spillman D. The duffy-binding-like domain 1 of the Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is a heparan sulfate ligand that requires 12-mers for binding. [Submitted] V. Heddini A, Obiero J, Barragan A, Kai O, Wahlgren M, Marsh K. Plasmodium falciparum-infected erythrocytes of children with servere malaria bind to multiple receptors. [Submitted] VI. Chen Q, Heddini A, Barragan A, Fernandez V, Pearce SFA, Wahlgren M. The semi-conserved head structure of Plasmodium falciparum erythrocyte membrane protein 1 mediates binding to multiple independent host receptors. [Submitted] VII. Barragan A, Kremsner P, Wahlgren M, Carlson J (2000). Blood group A antigen is a co-receptor in Plasmodium falciparum rosetting. Infection and Immunity. [Accepted] https://pubmed.ncbi.nlm.nih.gov/10768996
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».