Plasmodium berghei sporozoites in nonreplicative vacuoles are eliminated by a PI3P-mediated autophagy-independent pathway.

Bindschedler, Annina; Wacker, Rahel; Egli, Jessica; Eickel, Nina; Schmuckli-Maurer, Jacqueline; Franke-Fayard, Blandine M; Janse, Chris J; Heussler, Volker T. (2021). Plasmodium berghei sporozoites in nonreplicative vacuoles are eliminated by a PI3P-mediated autophagy-independent pathway. Cellular microbiology, 23(1), e13271. Wiley 10.1111/cmi.13271

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The protozoan parasite Plasmodium, causative agent of malaria, invades hepatocytes by invaginating the host cell plasma membrane and forming a parasitophorous vacuole membrane (PVM). Surrounded by this PVM, the parasite undergoes extensive replication. Parasites inside a PVM provoke the Plasmodium-associated autophagy-related (PAAR) response. This is characterized by a long-lasting association of the autophagy marker protein LC3 with the PVM, which is not preceded by phosphatidylinositol 3-phosphate (PI3P)-labelling. Prior to productive invasion, sporozoites transmigrate several cells and here we describe that a proportion of traversing sporozoites become trapped in a transient traversal vacuole, provoking a host cell response that clearly differs from the PAAR response. These trapped sporozoites provoke PI3P-labelling of the surrounding vacuolar membrane immediately after cell entry, followed by transient LC3-labelling and elimination of the parasite by lysosomal acidification. Our data suggest that this PI3P response is not only restricted to sporozoites trapped during transmigration but also affects invaded parasites residing in a compromised vacuole. Thus, host cells can employ a pathway distinct from the previously described PAAR response to efficiently recognize and eliminate Plasmodium parasites. This article is protected by copyright. All rights reserved.

Item Type:

Journal Article (Original Article)

Division/Institute:

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

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Bindschedler, Annina Flavia, Schmuckli, Jacqueline, Heussler, Volker

Subjects:

500 Science > 570 Life sciences; biology

ISSN:

1462-5822

Publisher:

Wiley

Funders:

[42] Schweizerischer Nationalfonds

Language:

English

Submitter:

Volker Heussler

Date Deposited:

02 Nov 2020 11:36

Last Modified:

05 Dec 2022 15:41

Publisher DOI:

10.1111/cmi.13271

PubMed ID:

32979009

BORIS DOI:

10.7892/boris.147067

URI:

https://boris.unibe.ch/id/eprint/147067

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