Influence of aging on murine neutrophil and macrophage function against Candida albicans
Influence of aging on murine neutrophil and macrophage function against Candida albicans
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DOI：
10.1111/j.1574-695x.2008.00418.x
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发表时间：
2008-07-01
影响因子：
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通讯作者：
Gil, Maria Luisa
中科院分区：
文献类型：
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作者：
Murciano, Celia;Yanez, Alberto;Gil, Maria Luisa
本小组之前的研究表明，老年C57BL/6小鼠对白色念珠菌的先天和适应性免疫反应发生改变，更容易发生全身性原发性念珠菌病。在这项工作中，我们使用幼龄（2-3月龄）和老年（18-20月龄）C57BL/6小鼠，在体外研究衰老对(1)中性粒细胞和巨噬细胞的杀真菌活性的影响，(2)常驻腹膜巨噬细胞对白色念珠菌的反应产生的细胞因子，(3)常驻腹膜巨噬细胞表面toll样受体（TLR） 2表达的影响。我们的研究结果表明，随着年龄的增长，小鼠吞噬细胞具有良好的杀菌活性。在体外实验中，老年小鼠与年轻小鼠相比，纯化的（CD11b(+)）腹腔巨噬细胞对白色念珠菌酵母菌和菌丝的促炎细胞因子(IL-6、IL-1 β、肿瘤坏死因子α和趋化因子（mmp -2）的产生明显降低。然而，巨噬细胞对白色念珠菌的反应产生的IL-10在幼年和老年动物中是相似的。此外，衰老巨噬细胞中TLR2表面的基线表达水平低于对照巨噬细胞。综上所述，这些数据表明老年小鼠对白色念珠菌播散性感染的易感性增加与TLR2表达缺陷和细胞因子产生缺陷有关，但与杀真菌活性受损无关。
Previous work by our group showed that aged C57BL/6 mice develop an altered innate and adaptive immune response to Candida albicans and are more susceptible to systemic primary candidiasis. In this work, we used young (2-3 months old) and aged (18-20 months old) C57BL/6 mice to study in vitro the influence of aging on (1) the fungicidal activity of neutrophils and macrophages, (2) the production of cytokines by resident peritoneal macrophages in response to C. albicans, and (3) cell surface Toll-like receptor (TLR) 2 expression on resident peritoneal macrophages. Our results indicate that murine phagocytes have a fungicidal activity well preserved with aging. In vitro production of proinflammatory cytokines (IL-6, IL-1 beta, and tumor necrosis factor-alpha and chemokines (MIP-2) by purified (CD11b(+)) peritoneal macrophages in response to yeasts and hyphae of C. albicans was significantly lower in aged mice as compared with young mice. However, the production of IL-10 by macrophages, in response to C. albicans, was similar in both young and aged animals. Moreover, baseline TLR2 surface expression level was lower on aged macrophages than on control macrophages. Taken together, these data indicate that the increased susceptibility to C. albicans disseminated infections in aged mice is correlated with defects in TLR2 expression and in cytokine production, but not with an impaired fungicidal activity.