A spatiotemporally resolved single-cell atlas of the Plasmodium liver stage

被引:0
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作者
Amichay Afriat
Vanessa Zuzarte-Luís
Keren Bahar Halpern
Lisa Buchauer
Sofia Marques
Ângelo Ferreira Chora
Aparajita Lahree
Ido Amit
Maria M. Mota
Shalev Itzkovitz
机构
[1] Weizmann Institute of Science,Department of Molecular Cell Biology
[2] Faculdade de Medicina da Universidade de Lisboa,Instituto de Medicina Molecular João Lobo Antunes
[3] Weizmann Institute of Science,Department of Systems Immunology
来源
Nature | 2022年 / 611卷
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摘要
Malaria infection involves an obligatory, yet clinically silent liver stage1,2. Hepatocytes operate in repeating units termed lobules, exhibiting heterogeneous gene expression patterns along the lobule axis3, but the effects of hepatocyte zonation on parasite development at the molecular level remain unknown. Here we combine single-cell RNA sequencing4 and single-molecule transcript imaging5 to characterize the host and parasite temporal expression programmes in a zonally controlled manner for the rodent malaria parasite Plasmodium berghei ANKA. We identify differences in parasite gene expression in distinct zones, including potentially co-adaptive programmes related to iron and fatty acid metabolism. We find that parasites develop more rapidly in the pericentral lobule zones and identify a subpopulation of periportally biased hepatocytes that harbour abortive infections, reduced levels of Plasmodium transcripts and parasitophorous vacuole breakdown. These ‘abortive hepatocytes’, which appear predominantly with high parasite inoculum, upregulate immune recruitment and key signalling programmes. Our study provides a resource for understanding the liver stage of Plasmodium infection at high spatial resolution and highlights the heterogeneous behaviour of both the parasite and the host hepatocyte.
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页码:563 / 569
页数:6
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