Distribution and Interaction of Murine Pulmonary Phagocytes in the Naive and Allergic Lung
Distribution and Interaction of Murine Pulmonary Phagocytes in the Naive and Allergic Lung
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DOI：
10.3389/fimmu.2018.01046
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发表时间：
2018-05-16
影响因子：
7.3
通讯作者：
Koenig, Peter
中科院分区：
文献类型：
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作者：
Hoffmann, Franziska M.;Berger, Johann L.;Koenig, Peter
肺吞噬亚群（巨噬细胞/单核细胞和树突状细胞亚群）之间的分工已经在功能水平上进行了描述。然而，这些肺吞噬细胞是否也表现出独特的空间分布尚不清楚。为了分析肺间室的细胞分布和吞噬细胞亚群之间的联系，我们建立了一种基于免疫组织化学（IHC）的方法，基于CD11c、CD11b、MHC-II、Langerin和mPDCA-1的差异表达，清晰地原位鉴定小鼠肺吞噬细胞亚群。此外，我们还研究了抗原摄取的亚群特异性功能差异和过敏致敏后的空间变化。我们的染色可以区分肺泡巨噬细胞（AMs）、间质巨噬细胞（IM）亚群、CD11b(+) DC亚群、CD103(+) DC和浆细胞样DC （pDCs）。我们确定气道之间和气道周围的间质区域是IM/CD11b(+) DC/CD103(+) DC集群的区域，其中IMs （IM2）和CD103(+) DC的子集形成强烈的接触，在过敏致敏后减少。这些数据表明，两种细胞类型之间的功能相互作用，无论是在稳定状态下还是在抗原遭遇后，都会影响过敏或耐受性的发展。此外，我们观察到主要抗原摄取在AMs和IMs中，而不是DC亚群，不局限于气道和邻近区域。这将使未来的研究集中在免疫学相关的细胞相互作用上，并揭示哪些细胞在促炎免疫反应或耐受性之间打破平衡。
The division of labor between pulmonary phagocytic subsets [macrophage/monocyte and dendritic cell (DC) subpopulations] has been described at the functional level. However, whether these lung phagocytes also display unique spatial distribution remains unclear. Here, to analyze cellular distribution in lung compartments and contacts between phagocyte subpopulations, we established an immunohistochemistry (IHC)-based method to clearly identify murine lung phagocyte subsets in situ based on differential expression of CD11c, CD11b, MHC-II, Langerin and mPDCA-1. Furthermore, we investigated subset-specific functional differences in antigen uptake and spatial changes upon allergic sensitization. Our staining allowed the distinction between alveolar macrophages (AMs), interstitial macrophage (IM) subpopulations, CD11b(+) DC subpopulations, CD103(+) DCs, and plasmacytoid DCs (pDCs). We identified interstitial regions between airways and around airways as regions of IM/CD11b(+) DC/CD103(+) DC clusters, where a subset of IMs (IM2) and CD103(+) DCs formed intense contacts that decreased upon allergic sensitization. These data indicate functional interactions between both cell types either in steady state or after antigen encounter affecting the development of allergies or tolerance. Furthermore, we observed major antigen uptake in AMs and IMs rather than DC subpopulations that was not restricted to airways and adjacent areas. This will enable to focus future studies to immunologically relevant cellular interactions and to unravel which cells are tipping the balance between pro-inflammatory immune responses or tolerance.