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Deciphering host lysosome-mediated elimination of Plasmodium berghei liver stage parasites.
- Source :
-
Scientific reports [Sci Rep] 2019 May 28; Vol. 9 (1), pp. 7967. Date of Electronic Publication: 2019 May 28. - Publication Year :
- 2019
-
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.
- Subjects :
- Animals
Biomarkers metabolism
Gene Expression
Green Fluorescent Proteins genetics
Green Fluorescent Proteins metabolism
HeLa Cells
Hepatocytes immunology
Hepatocytes parasitology
Hepatocytes ultrastructure
Host-Parasite Interactions immunology
Humans
Hydrogen-Ion Concentration
Light
Liver immunology
Liver metabolism
Liver parasitology
Lysosomal Membrane Proteins genetics
Lysosomal Membrane Proteins immunology
Lysosomes ultrastructure
Malaria genetics
Malaria immunology
Malaria parasitology
Membrane Fusion
Photosensitizing Agents chemistry
Photosensitizing Agents metabolism
Plasmodium berghei growth & development
Plasmodium berghei ultrastructure
Primary Cell Culture
Sporozoites growth & development
Sporozoites ultrastructure
Transgenes
Vacuoles metabolism
Vacuoles ultrastructure
Hepatocytes metabolism
Host-Parasite Interactions genetics
Lysosomes metabolism
Malaria metabolism
Plasmodium berghei metabolism
Sporozoites metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 9
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 31138850
- Full Text :
- https://doi.org/10.1038/s41598-019-44449-z