Toxoplasma-proximal and distal control by GBPs in human macrophages

Daniel Fisch, Barbara Clough, Rabia Khan, Lyn Healy, Eva-Maria Frickel

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Abstract

Human guanylate binding proteins (GBPs) are key players of interferon-gamma (IFNγ)-induced cell intrinsic defense mechanisms targeting intracellular pathogens. In this study, we combine the well-established Toxoplasmagondii infection model with three in vitro macrophage culture systems to delineate the contribution of individual GBP family members to control this apicomplexan parasite. Use of high-throughput imaging assays and genome engineering allowed us to define a role for GBP1, 2 and 5 in parasite infection control. While GBP1 performs a pathogen-proximal, parasiticidal and growth-restricting function through accumulation at the parasitophorous vacuole of intracellular Toxoplasma, GBP2 and GBP5 perform a pathogen-distal, growth-restricting role. We further find that mutants of the GTPase or isoprenylation site of GBP1/2/5 affect their normal function in Toxoplasma control by leading to mis-localization of the proteins.

Original languageEnglish
Article numberftab058
JournalPathogens and disease
Volume79
Issue number9
Early online date21 Dec 2021
DOIs
Publication statusPublished - 7 Jan 2022

Bibliographical note

© The Author(s) 2021. Published by Oxford University Press on behalf of FEMS.

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