Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, OR 97239, USA.
Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, OR 97239, USA.
Cell Rep. 2020 May 19;31(7):107662. doi: 10.1016/j.celrep.2020.107662.
Increasing evidence suggests that deficient immune modulation and microbial infections underline neurodegeneration, but the mechanisms remain obscure. Here, we show that the G-protein-coupled receptor (GPCR) SRBC-48, which belongs to the class BC serpentine receptors, has a protective role in Caenorhabditis elegans dendrite degeneration caused by Pseudomonas aeruginosa infection. Our results indicate that SRBC-48 functions in a cell-autonomous manner in AWC neurons to protect against infection-associated dendrite degeneration. The absence of SRBC-48 results in a reduced lifespan caused by a pathogen infection early in life that induces dendrite degeneration. The decreased longevity in animals deficient in SRBC-48 is due to uncontrolled activation of immune genes, particularly those regulated by the FOXO family transcription factor DAF-16 that is part of the insulin/insulin-like growth factor (IGF)-1 receptor homolog DAF-2. These results reveal how an infection early in life can not only induce dendrite degeneration but also reduce lifespan.
越来越多的证据表明，免疫调节不足和微生物感染是神经退行性变的基础，但其中的机制仍不清楚。在这里，我们表明属于 B 类卷曲受体的 G 蛋白偶联受体（GPCR）SRBC-48 在铜绿假单胞菌感染引起的秀丽隐杆线虫树突退化中具有保护作用。我们的结果表明，SRBC-48 在 AWC 神经元中以细胞自主的方式发挥作用，以防止感染相关的树突退化。SRBC-48 的缺失导致病原体感染早期引发树突退化，从而导致寿命缩短。缺乏 SRBC-48 的动物的寿命缩短是由于免疫基因的失控激活引起的，特别是那些受 FOXO 家族转录因子 DAF-16 调节的基因，DAF-16 是胰岛素/胰岛素样生长因子（IGF-1）受体同源物 DAF-2 的一部分。这些结果揭示了生命早期的感染不仅可以诱导树突退化，还可以降低寿命。
