Host-pathogen interactions in the Plasmodium-infected mouse liver at spatial and single-cell resolution

Franziska Hildebrandt (), Miren Urrutia Iturritza, Christian Zwicker, Bavo Vanneste, Noémi Van Hul, Elisa Semle, Jaclyn Quin, Tales Pascini, Sami Saarenpää, Mengxiao He, Emma R. Andersson, Charlotte L. Scott, Joel Vega-Rodriguez, Joakim Lundeberg and Johan Ankarklev ()
Additional contact information
Franziska Hildebrandt: SE-106 91
Miren Urrutia Iturritza: SE-106 91
Christian Zwicker: Ghent University
Bavo Vanneste: Ghent University
Noémi Van Hul: SE-171 77
Elisa Semle: SE-106 91
Jaclyn Quin: SE-106 91
Tales Pascini: Rm 2E20A
Sami Saarenpää: KTH Royal Institute of Technology
Mengxiao He: KTH Royal Institute of Technology
Emma R. Andersson: SE-171 77
Charlotte L. Scott: Ghent University
Joel Vega-Rodriguez: Rm 2E20A
Joakim Lundeberg: KTH Royal Institute of Technology
Johan Ankarklev: SE-106 91

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: Abstract 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.

Date: 2024
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DOI: 10.1038/s41467-024-51418-2

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