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

Abstract:

: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.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Niklaus L,Agop-Nersesian C,Schmuckli-Maurer J,Wacker R,Grünig V,Heussler VT

doi

10.1038/s41598-019-44449-z

subject

Has Abstract

pub_date

2019-05-28 00:00:00

pages

7967

issue

1

issn

2045-2322

pii

10.1038/s41598-019-44449-z

journal_volume

9

pub_type

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