Horn Lucas, Leips Jeff, Starz-Gaiano Michelle
Department of Biological Sciences, University of Maryland Baltimore County, Baltimore, MD, 21250, USA.
Aging Cell. 2014 Aug;13(4):719-28. doi: 10.1111/acel.12227. Epub 2014 May 14.
Most multicellular organisms show a physiological decline in immune function with age. However, little is known about the mechanisms underlying these changes. We examined Drosophila melanogaster, an important model for identifying genes affecting innate immunity and senescence, to explore the role of phagocytosis in age-related immune dysfunction. We characterized the localized response of immune cells at the dorsal vessel to bacterial infection in 1-week- and 5-week-old flies. We developed a quantitative phagocytosis assay for adult Drosophila and utilized this to characterize the effect of age on phagocytosis in transgenic and natural variant lines. We showed that genes necessary for bacterial engulfment in other contexts are also required in adult flies. We found that blood cells from young and old flies initially engulf bacteria equally well, while cells from older flies accumulate phagocytic vesicles and thus are less capable of destroying pathogens. Our results have broad implications for understanding how the breakdown in cellular processes influences immune function with age.
大多数多细胞生物随着年龄增长免疫功能会出现生理性衰退。然而，对于这些变化背后的机制我们知之甚少。我们研究了黑腹果蝇，它是用于鉴定影响先天免疫和衰老基因的重要模型，以探索吞噬作用在与年龄相关的免疫功能障碍中的作用。我们对1周龄和5周龄果蝇背血管处免疫细胞对细菌感染的局部反应进行了表征。我们开发了一种针对成年果蝇的定量吞噬试验，并利用该试验来表征年龄对转基因和自然变异品系吞噬作用的影响。我们表明，在其他情况下细菌吞噬所必需的基因在成年果蝇中也是必需的。我们发现，年轻果蝇和老年果蝇的血细胞最初吞噬细菌的能力相当，但老年果蝇的细胞会积累吞噬泡，因此破坏病原体的能力较弱。我们的研究结果对于理解细胞过程的崩溃如何随着年龄增长影响免疫功能具有广泛的意义。
