Cohen Olivia, Maru Parag, Liang Qinli, Saeij Jeroen P J
Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California Davis, Davis, California, USA.
Service de Maladies Infectieuses et Tropicales, CHU Toulouse, Toulouse, France.
Infect Immun. 2025 Aug 12;93(8):e0001025. doi: 10.1128/iai.00010-25. Epub 2025 Jul 3.
is an obligate intracellular protozoan parasite that can establish lifelong infections and cause severe disease in immunocompromised individuals. Interferon gamma (IFNγ) is a key host defense cytokine that induces a variety of toxoplasmacidal mechanisms. Recent CRISPR/Cas9 loss-of-function screens identified multiple genes important for fitness in IFNγ-stimulated cells. One consistent hit in several screens was the parasite surface antigen, SAG1. Here, we used CRISPR/Cas9 to generate a knockout strain and found that SAG1 is important for parasite fitness specifically in IFNγ-stimulated cells. Mechanistic studies revealed that host surface sialic acids are important for parasite attachment, especially in IFNγ-stimulated cells. SAG1-deficient parasites had reduced attachment efficiency, which was exacerbated in IFNγ-treated cells. These findings highlight the role of SAG1 in mediating robust parasite attachment, especially in the context of immune pressure.
是一种专性细胞内原生动物寄生虫，可建立终身感染并在免疫功能低下的个体中引起严重疾病。干扰素γ（IFNγ）是一种关键的宿主防御细胞因子，可诱导多种杀弓形虫机制。最近的CRISPR/Cas9功能丧失筛选确定了多个对IFNγ刺激细胞中的适应性很重要的基因。在几个筛选中一个一致的命中基因是寄生虫表面抗原SAG1。在这里，我们使用CRISPR/Cas9生成了一个敲除菌株，发现SAG1对寄生虫在IFNγ刺激细胞中的适应性特别重要。机制研究表明，宿主表面唾液酸对寄生虫附着很重要，尤其是在IFNγ刺激的细胞中。缺乏SAG1的寄生虫附着效率降低，在IFNγ处理的细胞中这种情况会加剧。这些发现突出了SAG1在介导强大的寄生虫附着中的作用，尤其是在免疫压力的背景下。
