In Caenorhabditis elegans, SHN-1 is the homologue of SHANK, a scaffolding protein. In this study, we determined the molecular basis for SHN-1/SHANK in the regulation of innate immune response to fungal infection. Mutation of shn-1 increased the susceptibility to Candida albicans infection and suppressed the innate immune response. After C. albicans infection for 6, 12, or 24 h, both transcriptional expression of shn-1 and SHN-1::GFP expression were increased, implying that the activated SHN-1 may mediate a protection mechanism for C. elegans against the adverse effects from fungal infection. SHN-1 acted in both the neurons and the intestine to regulate the innate immune response to fungal infection. In the neurons, GLR-1, an AMPA ionotropic glutamate receptor, was identified as the downstream target in the regulation of innate immune response to fungal infection. GLR-1 further positively affected the function of SER-7-mediated serotonin signaling and antagonized the function of DAT-1-mediated dopamine signaling in the regulation of innate immune response to fungal infection. Our study suggests the novel function of SHN-1/SHANK in the regulation of innate immune response to fungal infection. Our results further imply the crucial role of neurotransmitter signals in mediating the function of SHN-1/SHANK in regulating innate immune response to fungal infection.

中文翻译：

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SHN-1/SHANK 对秀丽隐杆线虫真菌感染的先天免疫反应的调节。

在秀丽隐杆线虫中，SHN-1 是支架蛋白 SHANK 的同系物。在这项研究中，我们确定了 SHN-1/SHANK 在调节对真菌感染的先天免疫反应中的分子基础。shn-1的突变增加了对白色念珠菌感染的易感性并抑制了先天免疫反应。白色念珠菌感染 6、12 或 24 小时后，shn-1 和 SHN-1::GFP 表达的转录表达均增加，这意味着激活的 SHN-1 可能介导了对秀丽隐杆线虫的保护机制对抗真菌感染的不利影响。SHN-1 在神经元和肠道中起作用，以调节对真菌感染的先天免疫反应。在神经元中，GLR-1 是一种 AMPA 离子型谷氨酸受体，被确定为调节对真菌感染的先天免疫反应的下游靶标。GLR-1 进一步积极影响 SER-7 介导的血清素信号传导的功能，并拮抗 DAT-1 介导的多巴胺信号传导在调节真菌感染的先天免疫反应中的功能。我们的研究表明 SHN-1/SHANK 在调节对真菌感染的先天免疫反应中的新功能。我们的结果进一步暗示了神经递质信号在调节 SHN-1/SHANK 调节对真菌感染的先天免疫反应的功能中的关键作用。