Toxoplasma-proximal and distal control by GBPs in human macrophages. Issue 9 (21st December 2021)

• Record Type: Journal Article
• Authors: Fisch, Daniel; Clough, Barbara; Khan, Rabia; Healy, Lyn; Frickel, Eva-Maria
• Is Part Of: Pathogens and disease. Volume 79:Issue 9(2021)
• Publication Date: 2021-12-21
• Subjects: guanylate binding protein -- Toxoplasma gondii -- GBP1 -- interferon -- macrophage; Medical microbiology -- Periodicals; Pathogenic microorganisms -- Periodicals; Communicable diseases -- Microbiology -- Periodicals; Communicable diseases -- Pathogenesis -- Periodicals; Host-parasite relationships -- Periodicals; Systems biology -- Periodicals; 616.904105
• DOI: 10.1093/femspd/ftab058
• Languages: English
• ISSNs: 2049-632X

Abstract

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 Toxoplasma gondii 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. Abstract : In human macrophages, guanylate binging protein 1, 2 and 5 (GBP1/2/5) control the growth of the parasite Toxoplasma gondii, with solely GBP1 targeting the parasite vacuole for elimination.