Related Experiment Video
Updated: Jun 13, 2026
Toxoplasma gondii Cyst Wall Formation in Activated Bone Marrow-derived Macrophages and Bradyzoite Conditions
Published on: August 12, 2010
Toxoplasma-proximal and distal control by GBPs in human macrophages
Daniel Fisch1,2, Barbara Clough1,2, Rabia Khan2
1Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, Edgbaston B15 2TT, UK.
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.
Insights
Human guanylate binding proteins (GBPs) are crucial for controlling intracellular pathogens like Toxoplasma gondii. This study reveals specific roles for GBP1, GBP2, and GBP5 in restricting parasite growth and infection.
Area of Science:
- Immunology
- Cell Biology
- Parasitology
Background:
- Guanylate binding proteins (GBPs) are integral to interferon-gamma (IFNγ)-induced cellular defenses against intracellular pathogens.
- Understanding the specific functions of individual GBP family members is crucial for elucidating host-pathogen interactions.
Purpose of the Study:
- To investigate the distinct roles of human guanylate binding proteins (GBPs) in controlling intracellular Toxoplasma gondii infection.
- To delineate the contribution of GBP1, GBP2, and GBP5 to host defense mechanisms against this apicomplexan parasite.
Main Methods:
- Utilized a Toxoplasma gondii infection model in three distinct in vitro macrophage culture systems.
- Employed high-throughput imaging assays and genome engineering techniques.
- Analyzed the localization and function of GBP mutants.
Main Results:
- Identified specific roles for GBP1, GBP2, and GBP5 in controlling Toxoplasma gondii infection.
- GBP1 exhibits a direct parasiticidal and growth-restricting function at the pathogen's vacuole.
- GBP2 and GBP5 contribute to parasite growth restriction through a pathogen-distal mechanism.
- Mutations in the GTPase or isoprenylation sites of GBP1/2/5 impair their function and lead to mis-localization.
Conclusions:
- GBP1, GBP2, and GBP5 are key effectors in the host's intrinsic immune response against Toxoplasma gondii.
- Protein localization and functional domains (GTPase, isoprenylation) are critical for GBP-mediated parasite control.
- This research provides insights into the molecular mechanisms of GBP action in host defense against intracellular parasites.
More Related Videos
09:52Genetic Manipulation in Δku80 Strains for Functional Genomic Analysis of Toxoplasma gondii
Published on: July 12, 2013
11:21Forward Genetics Screens Using Macrophages to Identify Toxoplasma gondii Genes Important for Resistance to IFN-γ-Dependent Cell Autonomous Immunity
Published on: March 12, 2015
