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| Status |
Public on Aug 20, 2022 |
| Title |
Plasmodium falciparum and TNF-a Differentially Regulate Inflammatory and Barrier Integrity Pathways in Human Brain Endothelial Cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Cerebral malaria is a severe complication of Plasmodium falciparum infection characterized by the loss of blood-brain barrier (BBB) integrity, which is associated with brain swelling and mortality in patients. P. falciparum-infected red blood cells and in!ammatory cytokines, like tumor necrosis factor alpha (TNF-a), have been implicated in the development of cerebral malaria, but it is still unclear how they contribute to the loss of BBB integrity. Here, a combination of transcriptomic analysis and cellular assays detecting changes in barrier integrity and endothelial activation were used to distinguish between the effects of P. falciparum and TNF-a on a human brain microvascular endothelial cell (HBMEC) line and in primary human brain microvascular endothelial cells. We observed that while TNF-a induced high levels of endothelial activation, it only caused a small increase in HBMEC permeability. Conversely, P. falciparum-infected red blood cells (iRBCLs) led to a strong increase in HBMEC permeability that was not mediated by cell death. Distinct transcriptomic pro"les of TNF-a and P. falciparum in HBMECs con"rm the differential effects of these stimuli, with the parasite preferentially inducing an endoplasmic reticulum stress response. Our results establish that there are fundamental differences in the responses induced by TNF-a and P. falciparum on brain endothelial cells and suggest that parasite-induced signaling is a major component driving the disruption of the BBB during cerebral malaria, proposing a potential target for much needed therapeutics.
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| Overall design |
Comparative gene expression profiling analysis of RNA-seq data for a human brain microvascular endothelial cell line incubated with media control, TNF-alpha, a lysate of control uninfected RBC or a lysate of Plasnodium falciparum-infected RBC.
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| Contributor(s) |
Zuniga M, Gomes C, Chen Z, Martinez C, Devlin JC, Loke P, Rodriguez A |
| Citation(s) |
36036514, 37788095 |
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| Submission date |
Aug 17, 2022 |
| Last update date |
Jan 02, 2024 |
| Contact name |
Ze Chen |
| Organization name |
NYU Grossman School of Medicine
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| Street address |
430 East 29th Street
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| City |
New York City |
| State/province |
New York |
| ZIP/Postal code |
10016 |
| Country |
USA |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (24)
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| GSM6470145 |
HBMEC_cells_control_rep1_lane1 [M1_S7_L001] |
| GSM6470146 |
HBMEC_cells_control_rep1_lane2 [M1_S7_L002] |
| GSM6470147 |
HBMEC_cells_control_rep2_lane1 [M2_S15_L001] |
| GSM6470148 |
HBMEC_cells_control_rep2_lane2 [M2_S15_L002] |
| GSM6470149 |
HBMEC_cells_control_rep3_lane1 [M3_S23_L001] |
| GSM6470150 |
HBMEC_cells_control_rep3_lane2 [M3_S23_L002] |
| GSM6470151 |
HBMEC_cells_TNF-alpha_rep1_lane1 [T1_S8_L001] |
| GSM6470152 |
HBMEC_cells_TNF-alpha_rep1_lane2 [T1_S8_L002] |
| GSM6470153 |
HBMEC_cells_TNF-alpha_rep2_lane1 [T2_S16_L001] |
| GSM6470154 |
HBMEC_cells_TNF-alpha_rep2_lane2 [T2_S16_L002] |
| GSM6470155 |
HBMEC_cells_TNF-alpha_rep3_lane1 [T3_S24_L001] |
| GSM6470156 |
HBMEC_cells_TNF-alpha_rep3_lane2 [T3_S24_L002] |
| GSM6470157 |
HBMEC_cells_RBC lysate_rep1_lane1 [R1_S1_L001] |
| GSM6470158 |
HBMEC_cells_RBC lysate_rep1_lane2 [R1_S1_L002] |
| GSM6470159 |
HBMEC_cells_RBC lysate_rep2_lane1 [R2_S9_L001] |
| GSM6470160 |
HBMEC_cells_RBC lysate_rep2_lane2 [R2_S9_L002] |
| GSM6470161 |
HBMEC_cells_RBC lysate_rep3_lane1 [R3_S17_L001] |
| GSM6470162 |
HBMEC_cells_RBC lysate_rep3_lane2 [R3_S17_L002] |
| GSM6470163 |
HBMEC_cells_P.falciparum_infected_RBC_lysate_rep1_lane1 [I1_S2_L001] |
| GSM6470164 |
HBMEC_cells_P.falciparum_infected_RBC_lysate_rep1_lane2 [I1_S2_L002] |
| GSM6470165 |
HBMEC_cells_P.falciparum_infected_RBC_lysate_rep2_lane1 [I2_S10_L001] |
| GSM6470166 |
HBMEC_cells_P.falciparum_infected_RBC_lysate_rep2_lane2 [I2_S10_L002] |
| GSM6470167 |
HBMEC_cells_P.falciparum_infected_RBC_lysate_rep3_lane1 [I3_S18_L001] |
| GSM6470168 |
HBMEC_cells_P.falciparum_infected_RBC_lysate_rep3_lane2 [I3_S18_L002] |
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| Relations |
| BioProject |
PRJNA870414 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE211439_processed_count.txt.gz |
676.4 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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