The Concern Foundation Laboratories at the Lautenberg Center for Immunology and Cancer Research, Institute for Medical Research Israel Canada (IMRIC), Hebrew University-Hadassah Medical School, Jerusalem, Israel.
mBio. 2024 Sep 11;15(9):e0116524. doi: 10.1128/mbio.01165-24. Epub 2024 Aug 7.
T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT) is an inhibitory receptor expressed by T and natural killer cells. Here, we used TIGIT knockout (KO) mice to demonstrate that mouse TIGIT directly interacts with . Reduced fungal growth and colonization were observed when TIGIT-KO splenocytes were co-cultured with compared to the wild type (WT). In a systemic candidiasis model, TIGIT-KO mice exhibited improved survival and reduced body weight loss compared to WT mice. Organ-specific fungal burden assessment revealed significantly lower fungal loads in the kidneys, spleen, and lungs of TIGIT-KO mice. Finally, we show that the agglutinin-like sequence proteins ALS6, ALS7, and ALS9 of are ligands for TIGIT and that the absence of these proteins abolishes the TIGIT effect . Our results identify the significance of TIGIT in modulating host defense against and highlight the potential therapeutic implications for infections.
Our results identify the significance of T cell immunoreceptor with immunoglobulin and ITIM domain in modulating host defense against and highlight the potential therapeutic implications for infections.
T 细胞免疫受体具有免疫球蛋白和免疫受体酪氨酸抑制基序（ITIM）结构域（TIGIT），是 T 细胞和自然杀伤细胞表达的抑制受体。在这里，我们使用 TIGIT 敲除（KO）小鼠来证明小鼠 TIGIT 可直接与 相互作用。与野生型（WT）相比，当 TIGIT-KO 脾细胞与 共培养时，观察到真菌生长和定植减少。在系统性念珠菌病模型中，与 WT 小鼠相比，TIGIT-KO 小鼠的存活率提高，体重减轻减少。器官特异性真菌负荷评估显示，TIGIT-KO 小鼠的肾脏、脾脏和肺部的真菌负荷明显降低。最后，我们表明 凝集素样序列蛋白 ALS6、ALS7 和 ALS9 是 TIGIT 的配体，并且这些蛋白的缺失会消除 TIGIT 的作用。我们的研究结果确定了 T 细胞免疫球蛋白和 ITIM 结构域在调节宿主防御中的重要性，为念珠菌感染的潜在治疗意义提供了新的见解。
我们的研究结果确定了 T 细胞免疫球蛋白和 ITIM 结构域在调节宿主防御中的重要性，为念珠菌感染的潜在治疗意义提供了新的见解。
