Host-pathogen interactions in the Plasmodium-infected mouse liver at spatial and single-cell resolution
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.
Authors
- C. Zwicker (ORCID: https://orcid.org/0000-0001-7724-1361)
- Mengxiao He (ORCID: https://orcid.org/0000-0001-5905-8467)
- Emma Andersson (ORCID: https://orcid.org/0000-0002-8608-625X)
- Johan Ankarklev (ORCID: https://orcid.org/0000-0003-3170-8493)
- Tales Vicari Pascini (ORCID: https://orcid.org/0000-0001-8759-0362)
- Joel Vega-Rodríguez (ORCID: https://orcid.org/0000-0002-9576-0058)
- Jaclyn Quin (ORCID: https://orcid.org/0000-0001-7757-7295)
- Sami Saarenpää (ORCID: https://orcid.org/0000-0003-4731-6857)
- Joakim Lundeberg (ORCID: https://orcid.org/0000-0003-4313-1601)
- Noémi Van Hul (ORCID: https://orcid.org/0000-0003-1410-8808)
- Charlotte L. Scott (ORCID: https://orcid.org/0000-0003-4914-6580)
- Franziska Hildebrandt (ORCID: https://orcid.org/0000-0002-2673-1704)
- Bavo Vanneste (ORCID: https://orcid.org/0000-0002-4152-5634)
- Miren Urrutia Iturritza (ORCID: https://orcid.org/0000-0002-3989-1803)
- Elisa Semle
Institutions
- National Institutes of Health (US)
- Stockholm University (SE)
- Science for Life Laboratory (SE)
- Karolinska Institutet (SE)
- Ghent University (BE)
- National Institute of Allergy and Infectious Diseases (US)
- VIB-UGent Center for Inflammation Research (BE)
- KTH Royal Institute of Technology (SE)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-08-19
- DOI
- https://doi.org/10.1038/s41467-024-51418-2
- Citations
- 18
- Primary Topic
- Aquaculture disease management and microbiota
- Type
- article
- Field-Weighted Citation Impact
- 4.33
Funders
- Jeanssons Stiftelser
- Swedish Foundation for International Cooperation in Research and Higher Education
- Svenska Sällskapet för Medicinsk Forskning
- Karolinska Institutet
- Knut och Alice Wallenbergs Stiftelse
- Vetenskapsrådet
- Stockholms Universitet
- Science for Life Laboratory
- National Institutes of Health
- Uppsala Multidisciplinary Center for Advanced Computational Science
- National Institute of Allergy and Infectious Diseases
- NHLBI Division of Intramural Research