Experimental Pneumology, Department of Pneumology, University Hospital Magdeburg, Health Campus Immunology, Infectiology and Inflammation, Otto-von-Guericke University, Magdeburg, Germany.
Infection Immunology Group, Institute of Medical Microbiology, Infection Control and Prevention, University Hospital Magdeburg, Health Campus Immunology, Infectiology and Inflammation, Otto-von-Guericke University, Magdeburg, Germany.
Front Immunol. 2024 Mar 11;15:1374670. doi: 10.3389/fimmu.2024.1374670. eCollection 2024.
Allergic asthma has been mainly attributed to T helper type 2 (Th2) and proinflammatory responses but many cellular processes remain elusive. There is increasing evidence for distinct roles for macrophage and dendritic cell (DC) subsets in allergic airway inflammation (AAI). At the same time, there are various mouse models for allergic asthma that have been of utmost importance in identifying key inflammatory pathways in AAI but that differ in the allergen and/or route of sensitization. It is unclear whether and how the accumulation and activation of specialized macrophage and DC subsets depend on the experimental model chosen for analyses.
In our study, we employed high-parameter spectral flow cytometry to comprehensively assess the accumulation and phenotypic alterations of different macrophage- and DC-subsets in the lung in an OVA- and an HDM-mediated mouse model of AAI.
We observed subset-specific as well as model-specific characteristics with respect to cell numbers and functional marker expression. Generally, alveolar as opposed to interstitial macrophages showed increased MHCII surface expression in AAI. Between the models, we observed significantly increased numbers of alveolar macrophages, CD103 DC and CD11b DC in HDM-mediated AAI, concurrent with significantly increased airway interleukin-4 but decreased total serum IgE levels. Further, increased expression of CD80 and CD86 on DC was exclusively detected in HDM-mediated AAI.
Our study demonstrates a model-specific involvement of macrophage and DC subsets in AAI. It further highlights spectral flow cytometry as a valuable tool for their comprehensive analysis under inflammatory conditions in the lung.
过敏性哮喘主要归因于辅助性 T 细胞 2（Th2）和促炎反应，但许多细胞过程仍不清楚。越来越多的证据表明，巨噬细胞和树突状细胞（DC）亚群在过敏性气道炎症（AAI）中具有不同的作用。与此同时，存在各种用于过敏性哮喘的小鼠模型，这些模型对于确定 AAI 中的关键炎症途径至关重要，但在过敏原和/或致敏途径上存在差异。目前尚不清楚选择用于分析的实验模型是否以及如何影响特定巨噬细胞和 DC 亚群的积累和激活。
在我们的研究中，我们采用高参数光谱流式细胞术全面评估 OVA 和 HDM 介导的 AAI 小鼠模型中肺内不同巨噬细胞和 DC 亚群的积累和表型改变。
我们观察到了与细胞数量和功能标记表达有关的亚群特异性和模型特异性特征。一般来说，与间质巨噬细胞相比，肺泡巨噬细胞在 AAI 中表现出更高的 MHCII 表面表达。在两种模型之间，我们观察到在 HDM 介导的 AAI 中，肺泡巨噬细胞、CD103 DC 和 CD11b DC 的数量显著增加，同时气道白细胞介素-4 显著增加，但总血清 IgE 水平降低。此外，仅在 HDM 介导的 AAI 中观察到 DC 上 CD80 和 CD86 的表达增加。
我们的研究表明，巨噬细胞和 DC 亚群在 AAI 中具有特定的参与。它进一步强调了光谱流式细胞术作为一种有价值的工具，可用于在肺部炎症条件下对其进行全面分析。
