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^*

^*Korrespondierende/r Autor/-in für diese Arbeit

16 Zitate (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.

Originalsprache	Englisch
Aufsatznummer	eadp6231
Zeitschrift	Science Immunology
Jahrgang	10
Ausgabenummer	106
DOIs	https://doi.org/10.1126/sciimmunol.adp6231
Publikationsstatus	Veröffentlicht - 04.2025

Fördermittel

We are thankful to E. Jacobsen for provision of EoCre mice. We acknowledge the services and support of CeMM BSF and Molecular Discovery Platform-Metabolomics. We thank U. Kaindl (Center for Anatomy and Cell Biology, Medical University of Vienna, Austria) for technical support. We thank all members of the Research Division Infection Biology for discussion and critical feedback throughout the duration of this project. This study was funded by the Austrian Science Fund (FWF; P31113-B30 and P36502-B) to P.S. and SFB-F061(P04) and to S.K. This research was funded in whole, or in part, by the Austrian Science Fund (FWF) (P36502 and P31113), a cOAlition S organization. For the purpose of open access, the authors will make the author accepted manuscript version available under a CC BY public copyright license. Acknowledgments: We are thankful to e. Jacobsen for provision of EoCre mice. We acknowledge the services and support of cemm BSF and molecular Discovery Platform– metabolomics. We thank u. Kaindl (center for Anatomy and cell Biology, medical university of Vienna, Austria) for technical support. We thank all members of the Research Division infection Biology for discussion and critical feedback throughout the duration of this project. Funding: this study was funded by the Austrian Science Fund (FWF; P31113-B30 and P36502-B) to P.S. and SFB-F061(P04) and to S.K. this research was funded in whole, or in part, by the Austrian Science Fund (FWF) (P36502 and P31113), a coAlition S organization. For the purpose of open access, the authors will make the author accepted manuscript version available under a cc By public copyright license. Author contributions: conceptualization: m.R. and P.S. investigation (experimental): m.R., A. Farhat, S.Z., l.P., A. Fokina, A. hladik, K.l., J.B., A.Z., m.i., t.K., m.e., and A.S. investigation (bioinformatics): A. hakobyan, J.m., n.n., n.F., V.D., and m.R. Funding acquisition: P.S. and S.K. Resources: S.K., P.S., J. Köhl, o.u., J. Kovarik, K.h., and A.V. Supervision: P.S. Writing— original draft: m.R. and P.S. Writing—review and editing: All authors. Competing interests: K.h. and A.V. are cofounders and shareholders of Aptarion Biotech and hold background iP on Aon-D21. K.h. and A.V. are also inventors on a background patent and divisional uS patents and patent applications around the c5a inhibitor Aon-D21. the other authors declare that they have no competing interests. Data and materials availability: the scRnA-seq, bulk RnA-seq, and AtAc-seq data have been deposited in geo under the following accession numbers: scRnA-seq (gSe287038), bulk RnA-seq (gSe286908), AtAc-seq (gSe287520). All original codes have been deposited at Zenodo and are accessible via the following links: scRnA-seq (https:// doi.org/10.5281/zenodo.14865685), bulk RnA-seq (https://doi.org/10.5281/zenodo.14697669), and AtAc-seq (https://doi.org/10.5281/zenodo.14699506). the metabolomics data are accessible at Zenodo via https://doi.org/10.5281/zenodo.14623014. tabulated data underlying the figures are provided in data file S8. All other data needed to evaluate the conclusions in the paper are present in the paper or the Supplementary materials.

Träger	Trägernummer
Molecular Discovery Platform-Metabolomics
CeMM BSF
Medizinische Universität Wien
Austrian Science Fund	SFB-F061, P04, P31113-B30, P36502-B, P31113, P36502

UN SDGs

Dieser Output leistet einen Beitrag zu folgendem(n) Ziel(en) für nachhaltige Entwicklung

SDG 3 – Gesundheit und Wohlergehen

Strategische Forschungsbereiche und Zentren

Forschungsschwerpunkt: Infektion und Entzündung - Zentrum für Infektions- und Entzündungsforschung Lübeck (ZIEL)

DFG-Fachsystematik

2.21-05 Immunologie
2.21-03 Medizinische Mikrobiologie und Mykologie, Hygiene, Molekulare Infektionsbiologie
2.22-22 Klinische Immunologie und Allergologie
2.22-13 Pneumologie, Thoraxchirurgie

Dokumente

10.1126/sciimmunol.adp6231

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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), Artikel eadp6231. https://doi.org/10.1126/sciimmunol.adp6231

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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",

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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, Jg. 10, Nr. 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

Fördermittel

UN SDGs

Strategische Forschungsbereiche und Zentren

DFG-Fachsystematik

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