The respiratory DC/macrophage network at steady-state and upon influenza infection in the swine biomedical model

The respiratory DC/macrophage network at steady-state and upon influenza infection in the swine biomedical model
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DOI:
10.1038/mi.2015.105
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发表时间:
2016-07-01
期刊:
影响因子:
8
通讯作者:
Bertho, N.
Bertho, N.
中科院分区:
医学1区
文献类型:
--
作者:
Maisonnasse, P.;Bouguyon, E.;Bertho, N.

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人和小鼠的呼吸道在解剖学和生理学上存在差异,这将有利于研究许多呼吸系统疾病的替代实验模型。猪已被公认为是一种有价值的生物医学模型,特别是在肺移植或囊性纤维化和流感感染等病理学方面。然而,人们对猪的呼吸道免疫系统缺乏了解。在这里,我们分离和研究了猪肺树突状细胞(DC)/巨噬细胞(M Theta S)六个群体:常规DC(CDC)1和CDC2,炎性单核细胞来源的DC(MODC),单核细胞来源的M theta S,以及间质和肺泡M theta S。这三个DC亚群具有迁移和幼稚的T细胞刺激能力。在人和小鼠体内观察到,猪cDC1和cDC2分别能诱导T辅助细胞(Th)1和Th2应答。有趣的是,正如在小鼠模型中观察到的那样,在流感感染后,猪肺中的moDC增加。猪CDC2有一些在人类中观察到而在小鼠中没有的特征,如Fc epsilon RIα和Langerin的表达,以及上皮内的定位。这项工作通过揭示猪和人肺DC/M theta网络的广泛相似性,突出了PIG作为DC/M theta功能的探索性模型和人类炎症肺病理的模型的相关性。
Human and mouse respiratory tracts show anatomical and physiological differences, which will benefit from alternative experimental models for studying many respiratory diseases. Pig has been recognized as a valuable biomedical model, in particular for lung transplantation or pathologies such as cystic fibrosis and influenza infection. However, there is a lack of knowledge about the porcine respiratory immune system. Here we segregated and studied six populations of pig lung dendritic cells (DCs)/macrophages (M theta s) as follows: conventional DCs (cDC) 1 and cDC2, inflammatory monocyte-derived DCs (moDCs), monocyte-derived M theta s, and interstitial and alveolar M theta s. The three DC subsets present migratory and naive T-cell stimulation capacities. As observed in human and mice, porcine cDC1 and cDC2 were able to induce T-helper (Th)1 and Th2 responses, respectively. Interestingly, porcine moDCs increased in the lung upon influenza infection, as observed in the mouse model. Pig cDC2 shared some characteristics observed in human but not in mice, such as the expression of FC epsilon RI alpha and Langerin, and an intra-epithelial localization. This work, by unraveling the extended similarities of the porcine and human lung DC/M theta networks, highlights the relevance of pig, both as an exploratory model of DC/M theta functions and as a model for human inflammatory lung pathologies.