Sifoglu Deniz, Pereira Bianca, DeGregory Christina, Shah Rahi, Maier Wolfgang, Guan Joanne, Clark Ian, Patel Dhaval, Ch'ng QueeLim, Alcedo Joy
Department of Biological Sciences, Wayne State University, Detroit, MI, USA.
Friedrich Miescher Institute for Biomedical Sciences, Basel, Switzerland.
bioRxiv. 2025 Aug 21:2025.08.15.670582. doi: 10.1101/2025.08.15.670582.
Distinct microbial environments exert diverse effects on the physiology and survival of the nematode . Here, we show that grown on two strains exhibit different survival dynamics. Wild-type on the B type OP50 exhibit more early deaths compared to on K-12 type CS180. These early deaths on OP50 are characterized by swollen pharynges (P-deaths) due to bacterial accumulation within the tissue. In contrast, animals on CS180 are more resistant to P-deaths. These bacteria-dependent differences in P-deaths depend on bacterial lipopolysaccharide structures and the activities of the neuropeptide neuromedin U receptor , which reduces P-deaths on OP50, but not on CS180. Surprisingly, however, promotes the opposite response when the insulin receptor DAF-2 has decreased activity - where now stimulates P-deaths on OP50, but again with no effect on CS180. We also find that acts in sensory neurons to promote its bi-directional effects on longevity, which depend on the FOXO transcription factor . regulates the expression of the insulin-like peptide , which further suggests a regulatory mechanism that maintains insulin receptor DAF-2 signaling at a suitable level. Thus, our studies reveal that serves to buffer the dynamic range of DAF-2 signaling, thereby optimizing pharyngeal health and survival in response to specific bacteria.
不同的微生物环境对线虫的生理机能和存活产生多样的影响。在此，我们表明在两种菌株上生长的线虫表现出不同的存活动态。与在K - 12型CS180上生长的线虫相比，在B型OP50上生长的野生型线虫出现更多早期死亡情况。在OP50上的这些早期死亡特征是由于组织内细菌积累导致咽部肿胀（P型死亡）。相比之下，在CS180上的线虫对P型死亡更具抗性。这些P型死亡中依赖细菌的差异取决于细菌脂多糖结构以及神经肽神经介素U受体的活性，该受体可减少OP50上的P型死亡，但对CS180上的P型死亡没有影响。然而，令人惊讶的是，当胰岛素受体DAF - 2活性降低时，神经介素U会引发相反的反应——此时神经介素U会刺激OP50上的P型死亡，但同样对CS180没有影响。我们还发现神经介素U在感觉神经元中发挥作用，以促进其对寿命的双向影响，这取决于FOXO转录因子。神经介素U调节胰岛素样肽的表达，这进一步提示了一种将胰岛素受体DAF - 2信号维持在适当水平的调节机制。因此，我们的研究揭示神经介素U起到缓冲DAF - 2信号动态范围的作用，从而根据特定细菌优化咽部健康和存活情况。
