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 |