NAD激活嗅觉受体1386以调节Plasmodium yoeliiYM感染中的I型干扰素反应
Yu-Chih Peng1, Jian Wu1, Xiao He1
1Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Disease, NIH, Rockville, MD 20852.
概括
嗅觉受体 (Olfrs) 在疟疾免疫力中发挥作用. Olfr1386调节I型干扰素反应,其配体尼古丁胺胺氨基二核酸 (NAD) 影响在Plasmodium yoelii感染期间的免疫信号.
科学领域:
- 免疫学 免疫学 免疫学
- 遗传学 是一个遗传学.
- 寄生虫学的寄生虫学
背景情况:
- 嗅觉受体 (Olfrs),通常在感觉神经元上,也存在于各种组织中,影响细胞功能和免疫反应.
- 奥尔弗斯在宿主-病原体相互作用中的作用,特别是在疟疾等寄生虫感染期间,仍然在很大程度上未被探索.
研究的目的:
- 在疟疾寄生虫感染的背景下研究嗅觉受体的表达和功能.
- 为了确定参与宿主免疫反应的特定Olfrs及其在Plasmodium感染期间的潜在连接体.
主要方法:
- 在小鼠脏中对Olfr基因表达的分析和与Plasmodium yoelii遗传位点的相关性.
- 使用HEK293T和RAW264.7细胞进行功能测试,以评估Olfr1386介导的免疫信号 (IFN-β,NF-κB).
- 编辑CRISPR/Cas9基因以产生Olfr1386-缺乏的小鼠用于感染研究.
- 对于Olfr1386.8的连接体查和代谢物识别 (NAD).
主要成果:
- 多个Olfr基因在脏中表达,并与疟疾易感位置相关联.
- Olfr1386表达增强了IFN-β和NF-κB信号通路,涉及关键的免疫激酶.
- 缺乏Olfr1386的小鼠表现出降低了I型干扰素水平,并增加了对P. yoelii感染的存活率.
- 尼古丁胺胺氨基二核酸 (NAD) 被确定为一种潜在的Olfr1386连接体,激活免疫反应.
结论:
- 嗅觉受体,包括Olfr1386,与宿主对疟疾的免疫反应有关.
- 在感染Plasmodium时,Olfr1386在调节I型干扰素产生的过程中起着至关重要的作用.
- 鉴定NAD作为Olfr1386连接体,为了解寄生虫疾病中的免疫调节开辟了新的途径.
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