Kravets Elisabeth, Poschmann Gereon, Hänsch Sebastian, Raba Veronica, Weidtkamp-Peters Stefanie, Degrandi Daniel, Stühler Kai, Pfeffer Klaus
Institute of Medical Microbiology and Hospital Hygiene, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
Institute of Molecular Medicine, Proteome Research, Medical Faculty and University Hospital, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.
PLoS One. 2025 Jan 24;20(1):e0316209. doi: 10.1371/journal.pone.0316209. eCollection 2025.
Guanylate binding proteins (GBPs) are large interferon-inducible GTPases, executing essential host defense activities against Toxoplasma gondii, an invasive intracellular apicomplexan protozoan parasite of global importance. T. gondii establishes a parasitophorous vacuole (PV) which shields the parasite from the host's intracellular defense mechanisms. Murine GBPs (mGBPs) recognize T. gondii PVs and assemble into supramolecular mGBP homo- and heterocomplexes that are required for the disruption of the membrane of PVs eventually resulting in the cell-autonomous immune control of vacuole-resident pathogens. We have previously shown that mGBP2 plays an important role in T. gondii immune control. Here, to unravel mGBP2 functions, we report Galectin-9 (Gal9) as a critical mGBP2 interaction partner engaged for immunity to T. gondii. Interestingly, Gal9 also accumulates and colocalizes with mGBP2 at the T. gondii PV. Furthermore, we could prove the requirement of Gal9 for growth control of T. gondii by CRISPR/Cas9 mediated gene editing. These discoveries clearly indicate that Gal9 is a crucial factor for the mGBP2-coordinated cell-autonomous host defense mechanism against T. gondii.
鸟苷酸结合蛋白（GBPs）是一类大型的干扰素诱导型GTP酶，在抵御弓形虫（一种具有全球重要性的侵入性细胞内顶复门原生动物寄生虫）的过程中发挥着重要的宿主防御作用。弓形虫会形成一个寄生泡（PV），使寄生虫免受宿主细胞内防御机制的影响。小鼠GBPs（mGBPs）能够识别弓形虫的PV，并组装成超分子mGBP同型和异型复合物，这些复合物是破坏PV膜所必需的，最终导致对泡内病原体的细胞自主免疫控制。我们之前已经表明mGBP2在弓形虫免疫控制中发挥重要作用。在此，为了阐明mGBP2的功能，我们报告半乳糖凝集素-9（Gal9）是参与弓形虫免疫的关键mGBP2相互作用伙伴。有趣的是，Gal9也会在弓形虫的PV处积累并与mGBP2共定位。此外，我们通过CRISPR/Cas9介导的基因编辑证明了Gal9对弓形虫生长控制的必要性。这些发现清楚地表明，Gal9是mGBP2协调的针对弓形虫的细胞自主宿主防御机制的关键因素。
