Systematic expression profiling of innate immune genes defines a complex pattern of immunosenescence in peripheral and intestinal leukocytes
Systematic expression profiling of innate immune genes defines a complex pattern of immunosenescence in peripheral and intestinal leukocytes
复制标题
DOI：
10.1038/sj.gene.6364454
复制
发表时间：
2008-03-01
影响因子：
5
通讯作者：
Schreiber, S.
中科院分区：
文献类型：
--
作者：
Rosenstiel, P.;Derer, S.;Schreiber, S.
免疫衰老的特征在于足够的免疫应答的定量下降，这使得老年个体特别容易受到细菌、病毒和真菌病原体的影响。虽然衰老适应性免疫系统的变化（例如，免疫球蛋白分泌减少）已被广泛表征，但先天免疫系统的改变仍然知之甚少。本研究的目的是系统地检测先天免疫基因和促炎细胞因子在不同年龄的受试者的外周血和肠道白细胞中的mRNA表达水平。在这两种情况下，全血样本和结肠活检中，大多数Toll样受体（TLR）和核苷酸结合和寡聚化结构域样受体（NLR）转录水平在老年受试者（90-99岁）中显著下调。与年轻人相比，老年人外周血和肠道白细胞的促炎细胞因子表达和/或分泌增加，结肠活检中核因子-κ B活化水平增加。在衰老过程中观察到的TLR和NLR的下调可能导致缺乏对入侵病原体或植物植物群的有效识别。这种效应导致异常的次级免疫细胞激活，并可能显著导致高龄患者的发病率和死亡率。
Immunosenescence is characterized by a quantitative decline of adequate immune responses, which renders the elderly individual particularly susceptible to bacterial, viral and fungal pathogens. Whereas changes of the aging adaptive immune system (for example, reduced immunoglobulin secretion) have been extensively characterized, alterations of the innate immune system are still poorly understood. The aim of the present study was to systematically examine mRNA expression levels of innate immune genes and proinflammatory cytokines in peripheral and intestinal leukocytes of subjects of different ages. In both, whole blood samples and in colonic biopsies most of the Toll-like receptors (TLRs) and nucleotide-binding and oligomerization domain-like receptors (NLRs) transcript levels were significantly downregulated in elderly subjects (90-99 years). Older individuals, when compared to the younger, exhibited an increased expression and/or secretion of proinflammatory cytokines by peripheral and intestinal leukocytes as well as an increased level of nuclear factor-kappa B activation in colonic biopsies. The observed downregulation of TLRs and NLRs during the aging process may contribute to the lack of effective recognition of invading pathogens or the commensal flora. This effect results in aberrant secondary immune cell activation and could significantly contribute to morbidity and mortality at advanced age.