Deciphering host lysosome-mediated elimination of Plasmodium berghei liver stage parasites.

Niklaus, Livia; Agop-Nersesian, C; Schmuckli-Maurer, Jacqueline; Wacker, Rahel; Grünig, V; Heussler, Volker (2019). Deciphering host lysosome-mediated elimination of Plasmodium berghei liver stage parasites. Scientific Reports, 9(1), p. 7967. Nature Publishing Group 10.1038/s41598-019-44449-z

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Liver stage Plasmodium parasites reside in a parasitophorous vacuole (PV) that associates with lysosomes. It has previously been shown that these organelles can have beneficial as well as harmful effects on the parasite. Yet it is not clear how the association of lysosomes with the parasite is controlled and how interactions with these organelles lead to the antagonistic outcomes. In this study we used advanced imaging techniques to characterize lysosomal interactions with the PV. In host cells harboring successfully developing parasites we observed that these interaction events reach an equilibrium at the PV membrane (PVM). In a population of arrested parasites, this equilibrium appeared to shift towards a strongly increased lysosomal fusion with the PVM witnessed by strong PVM labeling with the lysosomal marker protein LAMP1. This was followed by acidification of the PV and elimination of the parasite. To systematically investigate elimination of arrested parasites, we generated transgenic parasites that express the photosensitizer KillerRed, which leads to parasite killing after activation. Our work provides insights in cellular details of intracellular killing and lysosomal elimination of Plasmodium parasites independent of cells of the immune system.

Item Type:

Journal Article (Original Article)

Division/Institute:

08 Faculty of Science > Department of Biology > Institute of Cell Biology > Malaria
08 Faculty of Science > Department of Biology > Institute of Cell Biology

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Niklaus, Livia; Schmuckli, Jacqueline; Wacker, Rahel Corina and Heussler, Volker

Subjects:

500 Science > 570 Life sciences; biology

ISSN:

2045-2322

Publisher:

Nature Publishing Group

Funders:

[42] Schweizerischer Nationalfonds

Language:

English

Submitter:

Volker Heussler

Date Deposited:

09 Aug 2019 16:05

Last Modified:

22 Oct 2019 18:04

Publisher DOI:

10.1038/s41598-019-44449-z

PubMed ID:

31138850

BORIS DOI:

10.7892/boris.132432

URI:

https://boris.unibe.ch/id/eprint/132432

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