Proteomic identification of virulence-related factors in young and aging C. elegans infected with Pseudomonas aeruginosa
Proteomic identification of virulence-related factors in young and aging C. elegans infected with Pseudomonas aeruginosa
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DOI：
10.1016/j.jprot.2018.04.006
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发表时间：
2018-06-15
影响因子：
3.3
通讯作者：
Robinson, Rena A. S.
中科院分区：
文献类型：
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作者：
King, Christina D.;Singh, Daljeet;Robinson, Rena A. S.
区分免疫衰老与一般年龄相关衰退的分子机制知之甚少。我们通过将第1天和第5天的秀丽隐杆线虫成虫暴露于铜绿假单胞菌菌株PA 01（一种条件致病菌）来解决这一问题。第5天成人C.与第1天C相比，秀丽线虫表现出更大的感染脆弱性。优雅使用TMT 6-plex同量异序标记和还原二甲基化，我们确定了55种蛋白质，其水平在感染第1天和第5天成人后发生改变。蛋白质的水平变化，在这两个年龄段的感染反应强烈富集的运动功能，强调病原体回避机制的重要性。在第1天C.在线虫中，具有生殖功能的蛋白质高度富集，而第5天蠕虫显示代表应激反应途径的因子水平升高，如未折叠蛋白反应（UPR）和代谢功能。我们还发现PA 01感染与蛋白质羰基化水平升高有关，这是氧化应激的不可逆标志物。我们探索了UNC-60的功能，unc-60是一种细胞骨架蛋白，其水平会随着年龄和感染而改变，我们发现unc-60的突变体会缩短寿命。总的来说，我们的数据提供了新的见解年龄和免疫衰老之间的关系在metazoans.Significance：有差距，我们的知识有关如何老化影响一个有机体的病原体暴露的反应。In C.在线虫中，病原体暴露于铜绿假单胞菌PA 01导致寿命缩短，与第1天蠕虫相比，这在第5天更明显。蛋白质组对这种暴露具有年龄特异性反应，并且显著影响发育、生殖、代谢、蛋白质折叠/展开、运动和对压力的反应。这项研究解决了无脊椎动物衰老和免疫衰老之间的分子联系。
The molecular mechanisms that distinguish immunosenescence from general age-related decline are poorly understood. We addressed this by exposing Day 1 and Day 5 adults of Caenorhabditis elegans to Pseudomonas aeruginosa strain PA01, an opportunistic pathogen. Day 5 adult C. elegans exhibited greater vulnerability to infection as compared to Day 1 C. elegans. Using TMT6-plex isobaric labeling and reductive dimethylation, we identified 55 proteins whose levels were altered following infection of Day 1 and Day 5 adults. Proteins whose levels changed in response to infection at both ages were strongly enriched for locomotory functions underscoring the importance of pathogen avoidance mechanisms. In Day 1 C. elegans, proteins with reproductive functions were highly enriched, whereas, Day 5 worms showed elevated levels of factors representing stress response pathways such as unfolded protein response (UPR) and metabolic functions. We also found that PA01 infection is associated with elevated protein carbonylation, an irreversible marker for oxidative stress. We explored the function of UNC-60, a cytoskeletal protein whose levels were changed by both age and infection, and found that mutants of unc-60 have reduced lifespan. Overall, our data provide novel insights into the relationship between age and immunosenescence in metazoans.Significance: There are gaps in our knowledge pertaining to how aging influences an organism's response to pathogen exposure. In C. elegans, pathogen exposure to P. aeruginosa PA01 results in shortened lifespan, which is more pronounced in Day 5, compared to Day 1 adult worms. The proteome has age-specific responses to this exposure, and notably affects development, reproduction, metabolism, protein folding/unfolding, locomotion, and response to stress. This study addresses the molecular links between aging and immunosenescence in invertebrates.