Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Department of Chemical and Biomolecular Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
Cell Rep. 2023 Jun 27;42(6):112648. doi: 10.1016/j.celrep.2023.112648. Epub 2023 Jun 19.
Polysialic acid (polySia) is a post-translational modification of a select group of cell-surface proteins that guides cellular interactions. As the overall impact of changes in expression of this glycan on leukocytes during infection is not known, we evaluate the immune response of polySia-deficient ST8SiaIV mice infected with Streptococcus pneumoniae (Spn). Compared with wild-type (WT) mice, ST8SiaIV mice are less susceptible to infection and clear Spn from airways faster, with alveolar macrophages demonstrating greater viability and phagocytic activity. Leukocyte pulmonary recruitment, paradoxically, is diminished in infected ST8SiaIV mice, corroborated by adoptive cell transfer, microfluidic migration experiments, and intravital microscopy, and possibly explained by dysregulated ERK1/2 signaling. PolySia is progressively lost from neutrophils and monocytes migrating from bone marrow to alveoli in Spn-infected WT mice, consistent with changing cellular functions. These data highlight multidimensional effects of polySia on leukocytes during an immune response and suggest therapeutic interventions for optimizing immunity.
唾液酸化多醣（polySia）是一组特定细胞表面蛋白的翻译后修饰，可指导细胞间相互作用。由于目前尚不清楚这种聚糖在感染期间对白细胞表达变化的整体影响，我们评估了感染肺炎链球菌（Spn）的缺乏唾液酸化多醣的 ST8SiaIV 小鼠的免疫反应。与野生型（WT）小鼠相比，ST8SiaIV 小鼠对感染的敏感性较低，从气道中清除 Spn 的速度更快，肺泡巨噬细胞具有更高的活力和吞噬活性。相反，感染的 ST8SiaIV 小鼠中白细胞在肺部的募集减少，这一现象通过细胞转移、微流迁移实验和活体显微镜得到了证实，可能是由于 ERK1/2 信号的失调所致。在 Spn 感染的 WT 小鼠中，从骨髓迁移到肺泡的中性粒细胞和单核细胞中，polySia 逐渐丢失，这与不断变化的细胞功能一致。这些数据突出了 polySia 在免疫反应过程中对白细胞的多维度影响，并为优化免疫反应提供了治疗干预措施。
