Structural Damage in the C. elegans Epidermis Causes Release of STA-2 and Induction of an Innate Immune Response
Structural Damage in the C. elegans Epidermis Causes Release of STA-2 and Induction of an Innate Immune Response
复制标题
线虫表皮的结构损伤导致 STA-2 的释放并诱导先天免疫反应
DOI：
10.1016/j.immuni.2015.01.014
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发表时间：
2015-02-17
期刊：
影响因子：
32.4
通讯作者：
Zhang, Huimin
中科院分区：
文献类型：
--
作者：
Zhang, Yun;Li, Wenna;Zhang, Huimin
表皮不断遭遇破坏其结构的入侵，但表皮免疫系统是否利用受损结构作为危险信号来激活自卫尚不清楚。在这里，我们使用了秀丽隐杆线虫表皮模型，其中皮肤穿透性感染或损伤激活免疫防御和抗菌肽（AMP）的产生。通过系统性破坏每个结构组件，我们发现只有顶端半桥粒的干扰才会触发免疫反应和强大的 AMP 表达。表皮通过与 STAT 样蛋白相关的半桥粒识别结构损伤，该蛋白的破坏导致 STA-2 分子从半桥粒分离并转录 AMP。这种机制使表皮能够绕过某些信号放大，并在遭受广泛的结构损伤时直接触发 AMP 产生。总之，我们的研究结果揭示了上皮屏障检测危险和激活免疫防御的进化保守机制。
The epidermis constantly encounters invasions that disrupt its architecture, yet whether the epidermal immune system utilizes damaged structures as danger signals to activate self-defense is unclear. Here, we used a C. elegans epidermis model in which skin-penetrating infection or injury activates immune defense and antimicrobial peptide (AMP) production. By systemically disrupting each architectural component, we found that only disturbance of the apical hemidesmosomes triggered an immune response and robust AMP expression. The epidermis recognized structural damage through hemidesmosomes associated with a STAT-like protein, whose disruption led to detachment of STA-2 molecules from hemidesmosomes and transcription of AMPs. This machinery enabled the epidermis to bypass certain signaling amplification and directly trigger AMP production when subjected to extensive architectural damage. Together, our findings uncover an evolutionarily conserved mechanism for the epithelial barriers to detect danger and activate immune defense.