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Host-pathogen interactions in the Plasmodium-infected mouse liver at spatial and single-cell resolution
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- Hildebrandt, Franziska (författare)
- Stockholm Univ, Wenner Gren Inst, Mol Biosci, Svante Arrhenius Väg 20C, SE-10691 Stockholm, Sweden.
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- Iturritza, Miren Urrutia (författare)
- Stockholm Univ, Wenner Gren Inst, Mol Biosci, Svante Arrhenius Väg 20C, SE-10691 Stockholm, Sweden.
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- Zwicker, Christian (författare)
- Univ Ghent, Fac Sci, Dept Biomed Mol Biol, Ghent, Belgium.;VIB UGent Ctr Inflammat Res, Lab Myeloid Cell Biol Tissue Damage & Inflammat, Technolpk Zwijnaarde 71, B-9052 Ghent, Belgium.
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- Stockholm Univ, Wenner Gren Inst, Mol Biosci, Svante Arrhenius Väg 20C, SE-10691 Stockholm, Sweden Univ Ghent, Fac Sci, Dept Biomed Mol Biol, Ghent, Belgium.;VIB UGent Ctr Inflammat Res, Lab Myeloid Cell Biol Tissue Damage & Inflammat, Technolpk Zwijnaarde 71, B-9052 Ghent, Belgium. (creator_code:org_t)
- Springer Nature, 2024
- 2024
- Engelska.
- Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
- Tidskriftsartikel (refereegranskat)
Abstract
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- Upon infecting its vertebrate host, the malaria parasite initially invades the liver where it undergoes massive replication, whilst remaining clinically silent. The coordination of host responses across the complex liver tissue during malaria infection remains unexplored. Here, we perform spatial transcriptomics in combination with single-nuclei RNA sequencing over multiple time points to delineate host-pathogen interactions across Plasmodium berghei-infected liver tissues. Our data reveals significant changes in spatial gene expression in the malaria-infected tissues. These include changes related to lipid metabolism in the proximity to sites of Plasmodium infection, distinct inflammation programs between lobular zones, and regions with enrichment of different inflammatory cells, which we term 'inflammatory hotspots'. We also observe significant upregulation of genes involved in inflammation in the control liver tissues of mice injected with mosquito salivary gland components. However, this response is considerably delayed compared to that observed in P. berghei-infected mice. Our study establishes a benchmark for investigating transcriptome changes during host-parasite interactions in tissues, it provides informative insights regarding in vivo study design linked to infection and offers a useful tool for the discovery and validation of de novo intervention strategies aimed at malaria liver stage infection.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
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