Polysialylation controls immune function of myeloid cells in murine model of pneumococcal pneumonia.

Polysialylation controls immune function of myeloid cells in murine model of pneumococcal pneumonia.
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DOI:
10.1016/j.celrep.2023.112648
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发表时间:
2023-06-27
期刊:
影响因子:
8.8
通讯作者:
--
中科院分区:
生物学1区
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--
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聚唾液酸 (polySia) 是一组选定的细胞表面蛋白的翻译后修饰,可指导细胞相互作用。由于感染过程中这种聚糖表达变化对白细胞的总体影响尚不清楚,我们评估了感染肺炎链球菌(Spn)的polySia缺陷型ST8SiaIV−/−小鼠的免疫反应。与野生型 (WT) 小鼠相比,ST8SiaIV−/− 小鼠更不易受到感染,并且更快地从气道中清除 Spn,肺泡巨噬细胞表现出更强的活力和吞噬活性。矛盾的是,在受感染的 ST8SiaIV−/− 小鼠中,白细胞肺募集减少,过继细胞转移、微流体迁移实验和活体显微镜证实了这一点,并可能通过 ERK1/2 信号失调来解释。在 Spn 感染的 WT 小鼠中,PolySia 因中性粒细胞和单核细胞从骨髓迁移到肺泡而逐渐丢失,这与细胞功能的变化一致。这些数据强调了polySia在免疫反应过程中对白细胞的多维影响,并提出了优化免疫的治疗干预措施。 Shinde 等人比较了 ST8SiaIV−/− 和野生型小鼠的细胞。显示肺炎链球菌感染后,骨髓细胞表面聚唾液酸的逐渐丢失对细胞迁移和吞噬作用的影响。他们证明了这种聚糖对个体细胞类型的严格调控表达的重要性。
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. Comparing cells from ST8SiaIV−/− and wild-type mice, Shinde et al. show the impact of progressive loss of polysialic acid from the surface of myeloid cells on cell migration and phagocytosis after infection with Streptococcus pneumoniae. They demonstrate the importance of tightly regulated expression of this glycan on individual cell types.
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