Eosinophil innate immune memory after bacterial skin infection promotes allergic lung inflammation

Mariem Radhouani 1,2 , Asma Farhat 1,2 , Anna Hakobyan 2,3,4 , Sophie Zahalka 1,2 , Lisabeth Pimenov 1 , Alina Fokina 1 , Anastasiya Hladik 1 , Karin Lakovits 1 , Jessica Brösamlen 1 , Vojtech Dvorak 5 , Natalia Nunes 6 , Andreas Zech 7 , Marco Idzko 7 , Thomas Krausgruber 2,8 , Jörg Köhl 9,10, Ozge Uluckan 11, Jiri Kovarik 11, Kai Hoehlig 12, Axel Vater1 2, Margret Eckhard 13, Andy Sombke 13, Nikolaus Fortelny 6, Jörg Menche 2,3,4,14,15, Sylvia Knapp 1,16, Philipp Starkl 1 

Science Immunology
4 Apr 2025
Vol 10, Issue 106
DOI: 10.1126/sciimmunol.adp6231

Abstract
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 Staphylococcus aureus 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.

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