Eosinophil innate immune memory after bacterial skin infection promotes allergic lung inflammation
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 <i>Staphylococcus aureus</i> 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.
Authors
- Margret Eckhard (ORCID: https://orcid.org/0009-0009-5514-112X)
- Andreas Zech (ORCID: https://orcid.org/0000-0002-6928-0421)
- Andy Sombke (ORCID: https://orcid.org/0000-0001-7383-440X)
- Joerg Koehl (ORCID: https://orcid.org/0000-0003-1121-3178)
- А. А. Фокина (ORCID: https://orcid.org/0000-0001-5692-2483)
- Axel Vater (ORCID: https://orcid.org/0000-0003-4166-982X)
- Philipp Starkl (ORCID: https://orcid.org/0000-0001-7521-129X)
- Lisabeth Pimenov (ORCID: https://orcid.org/0000-0002-5154-4070)
- Kai Hoehlig (ORCID: https://orcid.org/0000-0002-4638-4826)
- Jörg Menche (ORCID: https://orcid.org/0000-0002-1583-6404)
- Karin Lakovits
- Jiří Kovařík
- Mariem Radhouani (ORCID: https://orcid.org/0000-0002-5739-9038)
- Thomas Krausgruber (ORCID: https://orcid.org/0000-0002-1374-0329)
- Sylvia Knapp (ORCID: https://orcid.org/0000-0001-9016-5244)
- Anna Hakobyan (ORCID: https://orcid.org/0000-0003-2667-6175)
- Nikolaus Fortelny (ORCID: https://orcid.org/0000-0003-4025-9968)
- Vojtech Dvorak (ORCID: https://orcid.org/0000-0002-9496-370X)
- Marco Idzko
- Özge Uluçkan (ORCID: https://orcid.org/0000-0001-9468-1211)
- Asma Farhat (ORCID: https://orcid.org/0000-0003-4669-9438)
- Sophie Zahalka (ORCID: https://orcid.org/0000-0003-0133-1672)
- Natália Nunes (ORCID: https://orcid.org/0000-0002-7247-4745)
- Anastasiya Hladik
- Jessica Brösamlen
Institutions
- Novartis (Switzerland) (CH)
- Cincinnati Children's Hospital Medical Center (US)
- University of Vienna (AT)
- Austrian Academy of Sciences (AT)
- Institute of Science and Technology Austria (AT)
- Austrian Research Institute for Artificial Intelligence (AT)
- University of Salzburg (AT)
- Max Perutz Labs (AT)
- Aptar (Germany) (DE)
- CeMM Research Center for Molecular Medicine (AT)
- Vienna Biocenter (AT)
- Medical University of Vienna (AT)
- University of Lübeck (DE)
Publication Details
- Journal
- Science Immunology
- Published
- 2025-04-04
- DOI
- https://doi.org/10.1126/sciimmunol.adp6231
- Citations
- 11
- Primary Topic
- IL-33, ST2, and ILC Pathways
- Type
- article
- Field-Weighted Citation Impact
- 8.77