Host-pathogen interactions in the Plasmodium-infected mouse liver at spatial and single-cell resolution.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
19 Aug 2024
19 Aug 2024
Historique:
received:
22
12
2023
accepted:
06
08
2024
medline:
20
8
2024
pubmed:
20
8
2024
entrez:
19
8
2024
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 39160174
doi: 10.1038/s41467-024-51418-2
pii: 10.1038/s41467-024-51418-2
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
7105Subventions
Organisme : Vetenskapsrådet (Swedish Research Council)
ID : VR 2021-05057
Organisme : Vetenskapsrådet (Swedish Research Council)
ID : VR 2019-01350
Organisme : Svenska Sällskapet för Medicinsk Forskning (Swedish Society for Medical Research)
ID : Stora Anslaaget
Organisme : Karolinska Institutet (Karolinska Institute)
ID : 2-195/2021
Informations de copyright
© 2024. The Author(s).
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