We recently reported that offspring of mice treated during pregnancy with the microbial-derived immunomodulator OM-85 manifest striking resistance to allergic airways inflammation, and localized the potential treatment target to fetal conventional dendritic cell (cDC) progenitors. Here, we profile maternal OM-85 treatment-associated transcriptomic signatures in fetal bone marrow, and identify a series of immunometabolic pathways which provide essential metabolites for accelerated myelopoiesis. Additionally, the cDC progenitor compartment displayed treatment-associated activation of the XBP1-ERN1 signalling axis which has been shown to be crucial for tissue survival of cDC, particularly within the lungs. Our forerunner studies indicate uniquely rapid turnover of airway mucosal cDCs at baseline, with further large-scale upregulation of population dynamics during aeroallergen and/or pathogen challenge. We suggest that enhanced capacity for XBP1-ERN1-dependent cDC survival within the airway mucosal tissue microenvironment may be a crucial element of OM-85-mediated transplacental innate immune training which results in postnatal resistance to airway inflammatory disease.

我们最近报道，在怀孕期间接受微生物源性免疫调节剂 OM-85 治疗的小鼠后代表现出对过敏性气道炎症的显着抵抗力，并将潜在的治疗目标定位于胎儿传统树突状细胞 (cDC) 祖细胞。在这里，我们分析了胎儿骨髓中母体 OM-85 治疗相关的转录组特征，并确定了一系列为加速骨髓生成提供必需代谢物的免疫代谢途径。此外，cDC祖细胞室显示出与治疗相关的XBP1-ERN1信号轴激活，这已被证明对于cDC的组织存活至关重要，特别是在肺内。我们的先行研究表明，气道粘膜 cDC 在基线时具有独特的快速周转，并且在气源性过敏原和/或病原体攻击期间群体动态进一步大规模上调。我们认为，气道粘膜组织微环境中 XBP1-ERN1 依赖性 cDC 存活能力的增强可能是 OM-85 介导的经胎盘先天免疫训练的关键要素，从而导致出生后对气道炎症性疾病的抵抗力。