IL-33 controls IL-22-dependent antibacterial defense by modulating the microbiota
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Published:2024-05-23
Issue:22
Volume:121
Page:
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ISSN:0027-8424
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Container-title:Proceedings of the National Academy of Sciences
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language:en
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Short-container-title:Proc. Natl. Acad. Sci. U.S.A.
Author:
Röwekamp Ivo1, Maschirow Laura1ORCID, Rabes Anne1, Fiocca Vernengo Facundo1, Hamann Lutz2ORCID, Heinz Gitta Anne3ORCID, Mashreghi Mir-Farzin3ORCID, Caesar Sandra1, Milek Miha4ORCID, Fagundes Fonseca Anna Carolina2ORCID, Wienhold Sandra-Maria1, Nouailles Geraldine1ORCID, Yao Ling1ORCID, Mousavi Soraya2, Bruder Dunja56ORCID, Boehme Julia D.56ORCID, Puzianowska-Kuznicka Monika78ORCID, Beule Dieter4, Witzenrath Martin19, , Löhning Max1011ORCID, Klose Christoph S. N.2ORCID, Heimesaat Markus M.2ORCID, Diefenbach Andreas2ORCID, Opitz Bastian19ORCID, Fuchs André, Engelmann Maximilian, Paul Gregor, Ayoub Mousa, Groehl Katharina, Riedl Katrin, Stolz Daiana, Bauer Wolfgang, Diehl-Wiesenecker Eva Corinna, von Wunsch-Rolshoven Terue Iris, Galtung Noah, Suttorp Norbert, Witzenrath Martin, Wildberg Christian, Pley Caitlin, Zessin Enrico, Schmager Sibylle, Schaaf Bernhard, Kremling Julius, Nickoleit-Bitzenberger Daniela, Azzaui Harun, Hower Martin, Hempel Frederik, Prebeg Katharina, Popkirova Kalina, Kolditz Martin, Schulte-Hubbert Bernhard, Langner Simona, Rohde Gernot, Bellinghausen Carla, Grϋnewaldt Achim, Endres Adrian, Frigerio Carlo, Fiedler Benno, Panning Marcus, Welte Tobias, Pink Isabell, Drick Nora, Fϋhner Thomas, van’t Klooster Mariet, Steinberg Tabea, Barten-Neiner Grit, Kröner Waldemar, Unruh Olesya, Adaskina Nina, Eberhardt Frank, Julius Christina, Illig Thomas, Klopp Norman, Pletz Mathias, Schleenvoigt Benjamin T., Bahrs Christina, Moeser Anne, Ankert Juliane, Sommerwerck Urte, Wintermantel Tobias, Drömann Daniel, Parschke Patrick, Franzen Klaas, Rupp Jan, Waldeck Frederike, Käding Nadja, Spinner Christoph, Erber Johanna, Voit Florian, Schneider Jochen, Falcone Marco, Tiseo Giusy, Heigener David, Hering Iris, Albrich Werner, Rassouli Frank, Wirth Benjamin, Neurohr Claus, Essig Andreas, Stenger Steffen, Wallner Michael, Burgmann Heinz, Traby Ludwig, Schubert Lorenz,
Affiliation:
1. Department of Infectious Diseases, Respiratory Medicine and Critical Care, Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin 13353, Germany 2. Institute of Microbiology, Infectious Diseases and Immunology, Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin 12203, Germany 3. German Rheumatism Research Center, a Leibniz Institute, Berlin 10117, Germany 4. Core Unit Bioinformatics, Berlin Institute of Health at Charité, Berlin 10117, Germany 5. Research Group Infection Immunology, Institute of Medical Microbiology and Hospital Hygiene, Health Campus Immunology, Infectiology and Inflammation, Otto-von-Guericke-University, Magdeburg 39120, Germany 6. Research Group Immune Regulation, Helmholtz Centre for Infection Research, Braunschweig 38124, Germany 7. Department of Human Epigenetics, Mossakowski Medical Research Institute, Polish Academy of Sciences, Warsaw 02-106, Poland 8. Department of Geriatrics and Gerontology, Medical Centre of Postgraduate Education, Warsaw 01-813, Poland 9. German center for lung research (DZL), Berlin 13353, Germany 10. Experimental Immunology and Osteoarthritis Research, Department of Rheumatology and Clinical Immunology, Charité–Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin 10117, Germany 11. Pitzer Laboratory of Osteoarthritis Research, German Rheumatism Research Center, a Leibniz Institute, Berlin 10117, Germany
Abstract
IL-22 plays a critical role in defending against mucosal infections, but how IL-22 production is regulated is incompletely understood. Here, we show that mice lacking IL-33 or its receptor ST2 (IL-1RL1) were more resistant to
Streptococcus pneumoniae
lung infection than wild-type animals and that single-nucleotide polymorphisms in
IL33
and
IL1RL1
were associated with pneumococcal pneumonia in humans. The effect of IL-33 on
S. pneumoniae
infection was mediated by negative regulation of IL-22 production in innate lymphoid cells (ILCs) but independent of ILC2s as well as IL-4 and IL-13 signaling. Moreover, IL-33’s influence on IL-22-dependent antibacterial defense was dependent on housing conditions of the mice and mediated by IL-33’s modulatory effect on the gut microbiota. Collectively, we provide insight into the bidirectional crosstalk between the innate immune system and the microbiota. We conclude that both genetic and environmental factors influence the gut microbiota, thereby impacting the efficacy of antibacterial immune defense and susceptibility to pneumonia.
Funder
Deutsche Forschungsgemeinschaft Bundesministerium für Bildung und Forschung EC | ERC | HORIZON EUROPE European Research Council Einstein Foundation Berlin
Publisher
Proceedings of the National Academy of Sciences
Cited by
2 articles.
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