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

Mariem Radhouani; Asma Farhat; Anna Hakobyan; Sophie Zahalka; Lisabeth Pimenov; Alina Fokina; Anastasiya Hladik; Karin Lakovits; Jessica Brösamlen; Vojtech Dvorak; Natalia Nunes; Andreas Zech; Marco Idzko; Thomas Krausgruber; Jörg Köhl; Ozge Uluckan; Jiri Kovarik; Kai Hoehlig; Axel Vater; Margret Eckhard; Andy Sombke; Nikolaus Fortelny; Jörg Menche; Sylvia Knapp; Philipp Starkl

doi:10.1126/sciimmunol.adp6231

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

Mariem Radhouani, Asma Farhat, Anna Hakobyan, Sophie Zahalka, Lisabeth Pimenov, Alina Fokina, Anastasiya Hladik, Karin Lakovits, Jessica Brösamlen, Vojtech Dvorak, Natalia Nunes, Andreas Zech, Marco Idzko, Thomas Krausgruber, Jörg Köhl, Ozge Uluckan, Jiri Kovarik, Kai Hoehlig, Axel Vater, Margret EckhardAndy Sombke, Nikolaus Fortelny, Jörg Menche, Sylvia Knapp, Philipp Starkl^*

^*Corresponding author for this work

16 Citations (Scopus)

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.

Original language	English
Article number	eadp6231
Journal	Science Immunology
Volume	10
Issue number	106
DOIs	https://doi.org/10.1126/sciimmunol.adp6231
Publication status	Published - 04.2025

Funding

Funders	Funder number
Molecular Discovery Platform-Metabolomics
CeMM BSF
University Hospital AKH Wien
Austrian Science Fund	SFB-F061, P04, P31113-B30, P36502-B, P31113, P36502

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Research Areas and Centers

Academic Focus: Center for Infection and Inflammation Research (ZIEL)

DFG Research Classification Scheme

2.21-05 Immunology
2.21-03 Medical Microbiology and Mycology, Hygiene, Molecular Infection Biology
2.22-22 Clinical Immunology and Allergology
2.22-13 Pneumology, Thoracic Surgery

Access to Document

10.1126/sciimmunol.adp6231

Cite this

Radhouani, M., Farhat, A., Hakobyan, A., Zahalka, S., Pimenov, L., Fokina, A., Hladik, A., Lakovits, K., Brösamlen, J., Dvorak, V., Nunes, N., Zech, A., Idzko, M., Krausgruber, T., Köhl, J., Uluckan, O., Kovarik, J., Hoehlig, K., Vater, A., ... Starkl, P. (2025). Eosinophil innate immune memory after bacterial skin infection promotes allergic lung inflammation. Science Immunology, 10(106), Article eadp6231. https://doi.org/10.1126/sciimmunol.adp6231

@article{9603b455258e4a8b9907f03b04367461,

title = "Eosinophil innate immune memory after bacterial skin infection promotes allergic lung inflammation",

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.",

author = "Mariem Radhouani and Asma Farhat and Anna Hakobyan and Sophie Zahalka and Lisabeth Pimenov and Alina Fokina and Anastasiya Hladik and Karin Lakovits and Jessica Br{\"o}samlen and Vojtech Dvorak and Natalia Nunes and Andreas Zech and Marco Idzko and Thomas Krausgruber and J{\"o}rg K{\"o}hl and Ozge Uluckan and Jiri Kovarik and Kai Hoehlig and Axel Vater and Margret Eckhard and Andy Sombke and Nikolaus Fortelny and J{\"o}rg Menche and Sylvia Knapp and Philipp Starkl",

note = "Publisher Copyright: Copyright {\textcopyright} 2025 The Authors, some rights reserved;",

year = "2025",

month = apr,

doi = "10.1126/sciimmunol.adp6231",

language = "English",

volume = "10",

journal = "Science Immunology",

issn = "2470-9468",

publisher = "American Association for the Advancement of Science",

number = "106",

}

Radhouani, M, Farhat, A, Hakobyan, A, Zahalka, S, Pimenov, L, Fokina, A, Hladik, A, Lakovits, K, Brösamlen, J, Dvorak, V, Nunes, N, Zech, A, Idzko, M, Krausgruber, T, Köhl, J, Uluckan, O, Kovarik, J, Hoehlig, K, Vater, A, Eckhard, M, Sombke, A, Fortelny, N, Menche, J, Knapp, S & Starkl, P 2025, 'Eosinophil innate immune memory after bacterial skin infection promotes allergic lung inflammation', Science Immunology, vol. 10, no. 106, eadp6231. https://doi.org/10.1126/sciimmunol.adp6231

TY - JOUR

T1 - Eosinophil innate immune memory after bacterial skin infection promotes allergic lung inflammation

AU - Radhouani, Mariem

AU - Farhat, Asma

AU - Hakobyan, Anna

AU - Zahalka, Sophie

AU - Pimenov, Lisabeth

AU - Fokina, Alina

AU - Hladik, Anastasiya

AU - Lakovits, Karin

AU - Brösamlen, Jessica

AU - Dvorak, Vojtech

AU - Nunes, Natalia

AU - Zech, Andreas

AU - Idzko, Marco

AU - Krausgruber, Thomas

AU - Köhl, Jörg

AU - Uluckan, Ozge

AU - Kovarik, Jiri

AU - Hoehlig, Kai

AU - Vater, Axel

AU - Eckhard, Margret

AU - Sombke, Andy

AU - Fortelny, Nikolaus

AU - Menche, Jörg

AU - Knapp, Sylvia

AU - Starkl, Philipp

PY - 2025/4

Y1 - 2025/4

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/105002829437

U2 - 10.1126/sciimmunol.adp6231

DO - 10.1126/sciimmunol.adp6231

M3 - Journal articles

C2 - 40184438

AN - SCOPUS:105002829437

SN - 2470-9468

VL - 10

JO - Science Immunology

JF - Science Immunology

IS - 106

M1 - eadp6231

ER -

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

Abstract

Funding

UN SDGs

Research Areas and Centers

DFG Research Classification Scheme

Access to Document

Other files and links

Fingerprint

Cite this