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| Status |
Public on Jun 03, 2024 |
| Title |
Host-Pathogen Interactions in the Plasmodium-Infected Mouse Liver at Spatial and Single-Cell Resolution (Spatial Transcriptomics 2k) |
| Organisms |
Plasmodium berghei ANKA; Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
During liver infection, the malaria parasite undergoes massive replication whilst remaining clinically silent. Spatial coordination of immune response regulation and metabolic zonation during malaria infection in the true tissue context remains unexplored. We perform spatial transcriptomics combined with snRNA-seq over multiple time points to delineate transcriptional programs of host-pathogen interactions across P. berghei-infected liver tissues. Our data suggest changes in gene expression related to lipid metabolism adjacent to infected hepatocytes, particularly modulation of the expression of genes involved in peroxisome proliferator-activated receptor pathway signaling. The data further indicates the presence of inflammatory hotspots with differential inflammation programs along the lobular axis in infected tissues. Additionally, upregulation of genes involved in inflammation is observed, but considerably delayed, in livers of control mice injected with mosquito salivary gland components. Our study establishes a benchmark for investigating host-parasite interactions, and can easily be implemented to validate de novo malaria drug and vaccine efforts.
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| Overall design |
For this study mice were infected with 400.000 sporozoites of P.berghei ANKA and collected after 12, 24 or 38h post-infection. Control mice were challenged with salivary gland lysate of the same number of mosquitos collected for P. berghei ANKA challenges. The full Spatial Transcriptomics 2k array protocol, including sequencing and computational analysis was performed for a total of 38 sections of which 23 were infected with Plasmodium berghei parasites and 15 challenged with mosquito salivary gland lysate. We analyzed 4 biological replicates for infected samples collected after 12h and 24h and 2 biological replicates for infected samples after 38h. For controls, we analyzed livers for 3, 3 and 2 biological replicates, respectively. Samples were selected based on sectioning and RNA quality.
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| Citation missing |
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| Submission date |
May 21, 2024 |
| Last update date |
Jun 03, 2024 |
| Contact name |
Franziska Hildebrandt |
| E-mail(s) |
franziska.hildebrandt@su.se
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| Phone |
0702186657
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| Organization name |
Stockholm University
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| Street address |
Svante Arrhenius Väg 20C, Stockholm
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| City |
Stockholm |
| ZIP/Postal code |
11418 |
| Country |
Sweden |
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| Platforms (2) |
| GPL34495 |
Illumina NextSeq 500 (Mus musculus; Plasmodium berghei ANKA) |
| GPL34496 |
NextSeq 2000 (Mus musculus; Plasmodium berghei ANKA) |
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| Samples (38)
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| Relations |
| BioProject |
PRJNA1114057 |
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