Essential Role of mGBP7 for Survival of Toxoplasma gondii Infection.
Nora SteffensCornelia Beuter-GuniaElisabeth KravetsArtur ReichLarissa LegewieKlaus PfefferDaniel DegrandiPublished in: mBio (2020)
Members of the murine guanylate-binding protein family (mGBP) are induced by interferon gamma (IFN-γ) and have been shown to be important factors in cell-autonomous immunity toward the intracellular pathogen Toxoplasma gondii Previously, we identified that mGBP2 mediates disruption of the parasitophorous vacuole membrane (PVM) and directly assaults the plasma membrane of the parasite. Here, we show that mGBP7-deficient mice are highly susceptible to T. gondii infection. This is demonstrated by the loss of parasite replication control, pronounced development of ascites, and death of the animals in the acute infection phase. Interestingly, live-cell microscopy revealed that mGBP7 recruitment to the PVM occurs after mGBP2 recruitment, followed by disruption of the PVM and T. gondii integrity and accumulation of mGBP7 inside the parasite. This study defines mGBP7 as a crucial effector protein in resistance to intracellular T. gondii IMPORTANCE Guanylate-binding proteins (GBPs) are induced by the inflammatory cytokine interferon gamma (IFN-γ) and have been shown to be important factors in the defense of the intracellular pathogen Toxoplasma gondii In previous studies, we showed that members of the mouse GBP family, such as mGBP2 and mGBP7, accumulate at the parasitophorous vacuole of T. gondii, which is the replicatory niche of the parasite. In this study, we show that mice deficient in mGBP7 succumb early after infection with T. gondii, showing a complete failure of resistance to the pathogen. On a molecular level, mGBP7 is found directly at the parasite, likely mediating its destruction.
Keyphrases
- toxoplasma gondii
- dendritic cells
- binding protein
- stem cells
- type diabetes
- single cell
- single molecule
- oxidative stress
- metabolic syndrome
- candida albicans
- reactive oxygen species
- high resolution
- liver failure
- skeletal muscle
- high throughput
- regulatory t cells
- bone marrow
- mass spectrometry
- mesenchymal stem cells
- small molecule
- adipose tissue
- high speed
- insulin resistance
- innate immune
- cell free
- label free
- cell therapy
- high fat diet induced
- mechanical ventilation