Toxoplasma-proximal and distal control by GBPs in human macrophages

Summary

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

Authors Fisch D, Clough B, Khan R, Healy L, Frickel EM
Journal Pathogens and disease
Publication Date 2022 Jan 7;79(9)
PubMed 34931666
PubMed Central PMC8752258
DOI 10.1093/femspd/ftab058

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