Radhouani Mariem, Farhat Asma, Hakobyan Anna, Zahalka Sophie, Pimenov Lisabeth, Fokina Alina, Hladik Anastasiya, Lakovits Karin, Brösamlen Jessica, Dvorak Vojtech, Nunes Natalia, Zech Andreas, Idzko Marco, Krausgruber Thomas, Köhl Jörg, Uluckan Ozge, Kovarik Jiri, Hoehlig Kai, Vater Axel, Eckhard Margret, Sombke Andy, Fortelny Nikolaus, Menche Jörg, Knapp Sylvia, Starkl Philipp
Department of Medicine I, Research Division Infection Biology, Medical University of Vienna, Vienna, Austria.
CeMM-Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
Sci Immunol. 2025 Apr 4;10(106):eadp6231. doi: 10.1126/sciimmunol.adp6231.
Microbial exposure at barrier interfaces drives development and balance of the immune system, but the consequences of local infections for systemic immunity and secondary inflammation are unclear. Here, we show that skin exposure to the bacterium persistently shapes the immune system of mice with specific impact on progenitor and mature bone marrow neutrophil and eosinophil populations. The infection-imposed changes in eosinophils were long-lasting and associated with functional as well as imprinted epigenetic and metabolic changes. Bacterial exposure enhanced cutaneous allergic sensitization and resulted in exacerbated allergen-induced lung inflammation. Functional bone marrow eosinophil reprogramming and pulmonary allergen responses were driven by the alarmin interleukin-33 and the complement cleavage fragment C5a. Our study highlights the systemic impact of skin inflammation and reveals mechanisms of eosinophil innate immune memory and organ cross-talk that modulate systemic responses to allergens.
屏障界面处的微生物暴露驱动免疫系统的发育和平衡，但局部感染对全身免疫和继发性炎症的影响尚不清楚。在这里，我们表明皮肤暴露于这种细菌会持续塑造小鼠的免疫系统，对祖细胞和成熟骨髓中性粒细胞及嗜酸性粒细胞群体有特定影响。感染引起的嗜酸性粒细胞变化是持久的，并与功能以及印记的表观遗传和代谢变化相关。细菌暴露增强了皮肤过敏致敏作用，并导致变应原诱导的肺部炎症加剧。功能性骨髓嗜酸性粒细胞重编程和肺部变应原反应由警报素白细胞介素-33和补体裂解片段C5a驱动。我们的研究突出了皮肤炎症的全身影响，并揭示了嗜酸性粒细胞固有免疫记忆和器官相互作用的机制，这些机制调节对变应原的全身反应。
