PD-1 deficiency impairs eosinophil recruitment to the tissue during Trichinella spiralis infection

Blockade of PD-1 may serve as a promising strategy in controlling pathogen infections through enhancing host immune cell function. Eosinophils are the essential components of the type 2 immune mechanism that function in host defense against helminth infections. Here we examine the role of PD-1 in eosinophilia in mice during T. spiralis infection. Unexpectedly, PD-1 deficient (PD-1-/-) mice developed higher muscle larvae loads and exacerbated disease compared to wild type mice. Further study showed that PD-1 deficiency impaired the recruitment of eosinophils into the parasite invaded tissue and their cytotoxicity to muscle larvae through reduced production of eosinophil-specific chemokines, and expression of adhesion molecules intergrin α4β7 and L-selectin on eosinophils and VCAM-1 on vascular endothelial cells after T. spiralis infection. The compromised T-helper 2 (Th2) cytokine response contributed to the impaired adhesion interactions involved in eosinophil migration in PD-1-/- mice infected with T. spiralis. Our data revealed the positive role of PD-1 in host defense against helminth infection by regulating the migration and trafficking of eosinophils to the infection site.程序性死亡受体1（PD-1）阻断或许可通过增强宿主免疫细胞功能，成为控制病原体感染的潜在策略。嗜酸性粒细胞是2型免疫机制的核心组分，在宿主抗蠕虫感染的免疫防御中发挥关键作用。本研究探究了旋毛形线虫（T. spiralis）感染期间，PD-1在小鼠嗜酸性粒细胞增多症中的作用。出乎意料的是，与野生型小鼠相比，PD-1缺陷（PD-1-/-）小鼠的肌肉幼虫负荷更高，病情更为严重。进一步研究显示，在旋毛形线虫感染后，PD-1缺陷会通过减少嗜酸性粒细胞特异性趋化因子的产生，以及降低嗜酸性粒细胞表面黏附分子整合素α4β7和L-选择素、血管内皮细胞表面血管细胞黏附分子1（VCAM-1）的表达，削弱嗜酸性粒细胞向寄生虫侵袭组织的募集及其对肌肉幼虫的细胞毒性。受损的2型辅助性T细胞（Th2）细胞因子应答，是旋毛形线虫感染的PD-1缺陷小鼠中嗜酸性粒细胞迁移相关黏附相互作用受损的重要原因。本研究数据揭示了PD-1通过调控嗜酸性粒细胞向感染部位的迁移与转运，在宿主抗蠕虫感染免疫防御中发挥的正向调控作用。