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通过 TIGIT 敲除增强抗感染免疫力。

Enhancing immunity against infections through TIGIT knockout.

机构信息

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.

出版信息

mBio. 2024 Sep 11;15(9):e0116524. doi: 10.1128/mbio.01165-24. Epub 2024 Aug 7.

Abstract

UNLABELLED

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.

IMPORTANCE

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.

摘要

未标记

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。

意义

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2768/11389390/f12fdbe56d93/mbio.01165-24.f001.jpg

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