Proteomic characterization of human proinflammatory M1 and anti-inflammatory M2 macrophages and their response to Candida albicans
Proteomic characterization of human proinflammatory M1 and anti-inflammatory M2 macrophages and their response to Candida albicans
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DOI：
10.1002/pmic.201300508
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发表时间：
2014-06-01
期刊：
影响因子：
3.4
通讯作者：
Gil, Concha
中科院分区：
文献类型：
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作者：
Antonio Reales-Calderon, Jose;Aguilera-Montilla, Noemi;Gil, Concha
响应于不同的刺激，巨噬细胞可以分化成促炎亚型（M1，经典活化的巨噬细胞）或获得抗炎表型（M2，替代活化的巨噬细胞）。白念珠菌是医院感染中最重要的机会致病真菌，在侵袭性感染的最初阶段，白念珠菌与中性粒细胞和巨噬细胞相互竞争。小鼠巨噬细胞对C.白色念珠菌的反应已被广泛研究，而人极化巨噬细胞的反应仍较少被表征。在这项研究中，我们的特点是人类M1和M2极化的巨噬细胞之间的蛋白质组差异，无论是在基础条件下，并在响应C。白念珠菌的蛋白质组学研究。这种蛋白质组学方法使我们能够确定M1和M2巨噬细胞之间最相关差异的代谢途径和细胞骨架重排组分。该分析揭示了果糖-1，6-二磷酸酶1，一种在细胞生成中的关键酶，在M1中上调，作为巨噬细胞极化的一种新的蛋白质标志物。关于对C.白色念珠菌，观察到偏振的M1至M2转换。这种M1到M2的转换可能通过减少特异性免疫反应的产生而促进念珠菌的致病性，从而增强真菌的存活和定植，或者相反，可能是宿主试图减少炎症和限制感染损害的一部分。
In response to different stimuli, macrophages can differentiate into either a pro-inflammatory subtype (M1, classically activated macrophages) or acquire an anti-inflammatory phenotype (M2, alternatively activated macrophages). Candida albicans is the most important opportunistic fungus in nosocomial infections, and it is contended by neutrophils and macrophages during the first steps of the invasive infection. Murine macrophages responses to C. albicans have been widely studied, whereas the responses of human-polarized macrophages remain less characterized. In this study, we have characterized the proteomic differences between human M1- and M2-polarized macrophages, both in basal conditions and in response to C. albicans, by quantitative proteomics (2DE). This proteomic approach allowed us to identify metabolic routes and cytoskeletal rearrangement components that are the most relevant differences between M1 and M2 macrophages. The analysis has revealed fructose-1,6-bisphosphatase 1, a critical enzyme in gluconeogenesis, up-regulated in M1, as a novel protein marker for macrophage polarization. Regarding the response to C. albicans, an M1-to-M2 switch in polarization was observed. This M1-to-M2 switch might contribute to Candida pathogenicity by decreasing the generation of specific immune responses, thus enhancing fungal survival and colonization, or instead, may be part of the host attempt to reduce the inflammation and limit the damage of the infection.