Radhouani, Mariem, Farhat, Asma, Hakobyan, Anna, Zahalka, Sophie, Pimenov, Lisabeth, Fokina, Alina, Hladik, Anastasiya, Lakovits, Karin, Zech, Andreas, Idzko, Marko, Krausgruber, Thomas, Uluckan, Ozge, Kovarik, Jiri, Hoehlig, Kai, Vater, Axel, Menche, Joerg, Knapp, Sylvia and Starkl, Philipp (2025) Eosinophil innate immune memory after bacterial skin infection promotes allergic lung inflammation. Science immunology, 10 (106). eadp6231. ISSN 2470-9468

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.

Item Type:	Article
Keywords:	Animals Immunity, Innate Mice Eosinophils Staphylococcus aureus Immunologic Memory Mice, Inbred C57BL Female Interleukin-33 Pneumonia Staphylococcal Skin Infections Trained Immunity
Date Deposited:	29 Apr 2025 00:45
Last Modified:	29 Apr 2025 00:45
URI:	https://oak.novartis.com/id/eprint/51136