Infection Immunology Group, Institute of Medical Microbiology and Hospital Hygiene, Otto-von-Guericke University, Magdeburg, Germany.
Immune Regulation Group, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Sci Rep. 2017 Jul 10;7(1):4972. doi: 10.1038/s41598-017-05212-4.
Airway epithelial cells (AECs) display remarkable plasticity in response to infectious stimuli and their functional adaptations are critical for antimicrobial immunity. However, the roles of AECs and humoral mediators to host defense in non-communicable lung inflammation remain elusive. We dissected pulmonary defense against Streptococcus pneumoniae in hosts with pre-existing inflammatory conditions (SPC-HAxTCR-HA mice). Lung tissue transcriptomics and bronchoalveolar lavage fluid (BALF) proteomics revealed an induction of humoral defense mechanisms in inflamed lungs. Accordingly, besides antibacterial proteins and complement components being overrepresented in inflamed lungs, elevated polymeric immunoglobulin receptor (pIgR)-expression in AECs correlated with increased secretory immunoglobulin (SIg) transport. Consequently, opsonization assays revealed augmented pneumococcal coverage by SIgs present in the BALF of SPC-HAxTCR-HA mice, which was associated with enhanced antipneumococcal resistance. These findings emphasize the immunologic potential of AECs as well as their central role in providing antibacterial protection and put forward pIgR as potential target for therapeutic manipulation in infection-prone individuals.
气道上皮细胞 (AECs) 在应对感染性刺激时表现出显著的可塑性，其功能适应对于抗菌免疫至关重要。然而，AECs 和体液介质在非传染性肺部炎症中的宿主防御作用仍不清楚。我们在存在先前炎症条件的宿主中（SPC-HAxTCR-HA 小鼠）剖析了肺部对肺炎链球菌的防御。肺组织转录组学和支气管肺泡灌洗液 (BALF) 蛋白质组学揭示了在炎症肺部中诱导了体液防御机制。因此，除了抗菌蛋白和补体成分在炎症肺部中过度表达外，AECs 中高分子量免疫球蛋白受体 (pIgR) 的表达增加与分泌型免疫球蛋白 (SIg) 转运的增加相关。因此，调理测定显示，存在于 SPC-HAxTCR-HA 小鼠 BALF 中的 SIg 增强了肺炎球菌的覆盖，这与抗肺炎球菌的抵抗力增强有关。这些发现强调了 AECs 的免疫学潜力及其在提供抗菌保护方面的核心作用，并提出了 pIgR 作为感染易感个体治疗干预的潜在靶点。
