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一个封闭的计算-实验循环识别了由于二元稳定性导致的巨功能障碍根源的代谢崩

Sunayana Malla, Deandra R Smith, Ashley M Peer

bioRxiv : the preprint server for biology

|January 16, 2026

概括

输送器ZIP8损失会破坏巨细胞代谢,并影响细菌感染控制. 恢复特定的代谢物,如酸盐可以增强免疫反应和细菌清除在缺乏条件下.

科学领域:

免疫学免疫学免疫学
代谢学代谢学代谢学
系统生物学系统生物学

背景情况:

对于免疫调节和屏障完整性至关重要.
在髓状细胞代谢和免疫中的作用尚未完全理解.

研究的目的:

研究ZIP8载体缺陷对巨细胞代谢和抗菌功能的影响.
为了阐明ZIP8损失在髓状细胞中的免疫代谢后果.

主要方法:

利用系统生物学方法与基于约束的建模.
在ZIP8淘汰赛 (Zip8 KO) 鼠标巨中分析了代谢干扰.
进行了基因组规模的代谢建模和流量分析.

主要成果:

ZIP8缺乏导致肺巨细胞的广泛代谢干扰,影响糖解,氨基酸代谢和线粒体功能.
Zip8 KO巨细胞显示营养吸收和能量代谢受损,Streptococcus pneumoniae感染加剧了这种情况.
代谢建模预测了矛盾的抑制,其次是过度补偿,导致免疫功能障碍和细菌清除受损.

结论:

ZIP8是巨细胞中免疫代谢恒常的关键调节者.
代谢物如酸和酸可以恢复免疫反应和细菌清除.
向ZIP8介导途径为与缺乏相关的免疫功能障碍提供了潜在的治疗策略.

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