Institute for Experimental Immunology and Imaging, Department of Immunodynamics, University Hospital Essen, Essen, Germany.
Kennedy Institute of Rheumatology, University of Oxford, Oxford, United Kingdom.
Front Immunol. 2023 Sep 18;14:1227191. doi: 10.3389/fimmu.2023.1227191. eCollection 2023.
is one of the main causes of community-acquired infections in the lung alveoli in children and the elderly. Alveolar macrophages (AM) patrol alveoli in homeostasis and under infectious conditions. However, the molecular adaptations of AM upon infections with are incompletely resolved.
We used a comparative transcriptomic and proteomic approach to provide novel insights into the cellular mechanism that changes the molecular signature of AM during lung infections. Using a tandem mass spectrometry approach to murine cell-sorted AM, we revealed significant proteomic changes upon lung infection with
AM showed a strong neutrophil-associated proteomic signature, such as expression of CD11b, MPO, neutrophil gelatinases, and elastases, which was associated with phagocytosis of recruited neutrophils. Transcriptomic analysis indicated intrinsic expression of CD11b by AM. Moreover, comparative transcriptomic and proteomic profiling identified CD11b as the central molecular hub in AM, which influenced neutrophil recruitment, activation, and migration.
In conclusion, our study provides novel insights into the intrinsic molecular adaptations of AM upon lung infection with and reveals profound alterations critical for effective antimicrobial immunity.
是导致儿童和老年人肺部肺泡社区获得性感染的主要原因之一。肺泡巨噬细胞（AM）在稳态和感染条件下巡逻肺泡。然而，感染 后 AM 的分子适应性仍不完全清楚。
我们使用比较转录组学和蛋白质组学方法，深入了解细胞机制，即在肺部感染过程中改变 AM 的分子特征。我们使用串联质谱法对小鼠细胞分选的 AM 进行分析，揭示了感染 后 AM 的显著蛋白质组变化。
AM 表现出强烈的中性粒细胞相关的蛋白质组学特征，如 CD11b、MPO、中性粒细胞明胶酶和弹性蛋白酶的表达，这与募集的中性粒细胞的吞噬作用有关。转录组分析表明 AM 内在表达 CD11b。此外，比较转录组学和蛋白质组学分析将 CD11b 确定为 AM 中的中央分子枢纽，它影响中性粒细胞的募集、激活和迁移。
总之，我们的研究提供了对 AM 在感染 后肺部感染时内在分子适应性的新见解，并揭示了对抗微生物免疫至关重要的深刻变化。
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