Department of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee 37232, United States.
Mass Spectrometry Research Center, Vanderbilt University, Nashville, Tennessee 37232, United States.
J Am Soc Mass Spectrom. 2024 Aug 7;35(8):1692-1701. doi: 10.1021/jasms.4c00089. Epub 2024 Jul 25.
Gangliosides play important roles in innate and adaptive immunity. The high degree of structural heterogeneity results in significant variability in ganglioside expression patterns and greatly complicates linking structure and function. Structural characterization at the site of infection is essential in elucidating host ganglioside function in response to invading pathogens, such as (). Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) enables high-specificity spatial investigation of intact gangliosides. Here, ganglioside structural and spatial heterogeneity within an -infected mouse kidney abscess was characterized. Differences in spatial distributions were observed for gangliosides of different classes and those that differ in ceramide chain composition and oligosaccharide-bound sialic acid. Furthermore, integrating trapped ion mobility spectrometry (TIMS) allowed for the gas-phase separation and visualization of monosialylated ganglioside isomers that differ in sialic acid type and position. The isomers differ in spatial distributions within the host-pathogen interface, where molecular patterns revealed new molecular zones in the abscess previously unidentified by traditional histology.
神经节苷脂在先天免疫和适应性免疫中发挥重要作用。其高度的结构异质性导致神经节苷脂表达模式的显著差异，极大地增加了结构与功能之间的联系的复杂性。在感染部位进行结构特征分析对于阐明宿主神经节苷脂在应对入侵病原体（如 ()）时的功能至关重要。基质辅助激光解吸/电离成像质谱 (MALDI IMS) 可实现对完整神经节苷脂的高特异性空间研究。在这里，对 () 感染的小鼠肾脓肿中的神经节苷脂的结构和空间异质性进行了表征。不同类别以及神经节苷脂的神经酰胺链组成和连接在唾液酸上的寡糖不同，其空间分布存在差异。此外，整合俘获离子淌度谱 (TIMS) 允许对在唾液酸类型和位置上存在差异的单唾液酸化神经节苷脂异构体进行气相分离和可视化。这些异构体在宿主-病原体界面的空间分布存在差异，其中分子模式揭示了先前通过传统组织学无法识别的脓肿中的新分子区。
