دورية أكاديمية
Transcriptional responses of brain endothelium to Plasmodium falciparum patient-derived isolates in vitro .
| العنوان: | Transcriptional responses of brain endothelium to Plasmodium falciparum patient-derived isolates in vitro . |
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| المؤلفون: | Askonas C; Pathogen Genomics Laboratory, Bioscience Program, Biological and Environmental Sciences and Engineering (BESE) Division, King Abdullah University of Science and Technology, Thuwal, Saudi Arabia., Storm J; Tropical Disease Biology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom., Camarda G; Tropical Disease Biology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom., Craig A; Tropical Disease Biology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom., Pain A; Pathogen Genomics Laboratory, Bioscience Program, Biological and Environmental Sciences and Engineering (BESE) Division, King Abdullah University of Science and Technology, Thuwal, Saudi Arabia. |
| المصدر: | Microbiology spectrum [Microbiol Spectr] 2024 Jul 02; Vol. 12 (7), pp. e0072724. Date of Electronic Publication: 2024 Jun 12. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: ASM Press Country of Publication: United States NLM ID: 101634614 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2165-0497 (Electronic) Linking ISSN: 21650497 NLM ISO Abbreviation: Microbiol Spectr Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, DC : ASM Press, 2013- |
| مواضيع طبية MeSH: | Plasmodium falciparum*/genetics , Plasmodium falciparum*/metabolism , Plasmodium falciparum*/physiology , Endothelial Cells*/parasitology , Endothelial Cells*/metabolism , Malaria, Falciparum*/parasitology , Malaria, Falciparum*/metabolism , Malaria, Cerebral*/parasitology , Malaria, Cerebral*/metabolism , Brain*/parasitology , Brain*/metabolism , Blood-Brain Barrier*/parasitology , Blood-Brain Barrier*/metabolism , Erythrocytes*/parasitology , Erythrocytes*/metabolism, Humans |
| مستخلص: | A hallmark of cerebral malaria (CM) is sequestration of Plasmodium falciparum -infected erythrocytes (IE) within the brain microvasculature. Binding of IE to endothelium reduces microvascular flow and, combined with an inflammatory response, perturbs endothelial barrier function, resulting in breakdown of the blood-brain barrier (BBB). Cytoadherence leads to activation of the endothelium and alters a range of cell processes affecting signaling pathways, receptor expression, coagulation, and disruption of BBB integrity. Here, we investigated whether CM-derived parasites elicit differential effects on human brain microvascular endothelial cells (HBMECs), as compared to uncomplicated malaria (UM)-derived parasites. Patient-derived IE from UM and CM clinical cases, as well as non-binding skeleton-binding protein 1 knockout parasites, were overlaid onto tumour necrosis factor (TNF)-activated HBMECs. Gene expression analysis of endothelial responses was performed using probe-based assays of a panel of genes involved in inflammation, apoptosis, endothelial barrier function, and prostacyclin synthesis pathway. We observed a significant effect on endothelial transcriptional responses in the presence of IE, yet there was no significant correlation between HBMEC responses and type of clinical syndrome (UM or CM). Furthermore, there was no correlation between HBMEC gene expression and both binding itself and level of IE binding to HBMECs, as we detected the same change in endothelial responses when employing both binding and non-binding parasites. Our results suggest that interaction of IE with endothelial cells in this co-culture model induces some endothelial responses that are independent of clinical origin and independent of the expression of the major variant antigen Plasmodium falciparum erythrocyte membrane protein 1 on the IE surface. Importance: Cerebral malaria (CM) is the most prevalent and deadly complication of severe Plasmodium falciparum infection. A hallmark of this disease is sequestration of P. falciparum -infected erythrocytes (IE) in brain microvasculature that ultimately results in breakdown of the blood-brain barrier. Here, we compared the effect of P. falciparum parasites derived from uncomplicated malaria (UM) and CM cases on the relative gene expression of human brain microvascular endothelial cells (HBMECs) for a panel of genes. We observed a significant effect on the endothelial transcriptional response in the presence of IE, yet there is no significant correlation between HBMEC responses and the type of clinical syndrome (UM or CM). Furthermore, there was no correlation between HBMEC gene expression and both binding itself and the level of IE binding to HBMECs. Our results suggest that interaction of IE with endothelial cells induces endothelial responses that are independent of clinical origin and not entirely driven by surface Plasmodium falciparum erythrocyte membrane protein 1 expression. Competing Interests: The authors declare no conflict of interest. |
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| معلومات مُعتمدة: | CRG6-3392.02 King Abdullah University of Science and Technology (KAUST) |
| فهرسة مساهمة: | Keywords: HBMEC; Plasmodium falciparum; cerebral malaria; cytoadherence; endothelium; gene expression |
| تواريخ الأحداث: | Date Created: 20240612 Date Completed: 20240702 Latest Revision: 20240711 |
| رمز التحديث: | 20240711 |
| مُعرف محوري في PubMed: | PMC11218514 |
| DOI: | 10.1128/spectrum.00727-24 |
| PMID: | 38864616 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2165-0497 |
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| DOI: | 10.1128/spectrum.00727-24 |