IL-33 controls IL-22-dependent antibacterial defense by modulating the microbiota

• 成果类型: Article
• 署名作者: Roewekamp, Ivo; Maschirow, Laura; Rabes, Anne; Vernengo, Facundo Fiocca; Hamann, Lutz; Heinz, Gitta Anne; Mashreghi, Mir- Farzin; Caesar, Sandra; Milek, Miha; Fonseca, Anna Carolina Fagundes; Wienhold, Sandra - Maria; Nouailles, Geraldine; Yao, Ling; Mousavi, Soraya; Bruder, Dunja; Boehme, Julia D.; Puzianowska-Kuznicka, Monika; Beule, Dieter; Witzenrath, Martin; Loehning, Max; Klose, Christoph S. N.; Heimesaat, Markus M.; Diefenbach, Andreas; Opitz, Bastian
• 署名单位: Free University of Berlin; Humboldt University of Berlin; Charite Universitatsmedizin Berlin; Free University of Berlin; Humboldt University of Berlin; Free University of Berlin; Humboldt University of Berlin; Charite Universitatsmedizin Berlin; Leibniz Association; Deutsches Rheuma-Forschungszentrum (DRFZ); Humboldt University of Berlin; Free University of Berlin; Charite Universitatsmedizin Berlin; Berlin Institute of Health; Otto von Guericke University; Helmholtz Association; Helmholtz-Center for Infection Research; Polish Academy of Sciences; Mossakowski Medical Research Institute of the Polish Academy of Sciences; Centre of Postgraduate Medical Education - Poland; Free University of Berlin; Humboldt University of Berlin; Charite Universitatsmedizin Berlin; Leibniz Association; Deutsches Rheuma-Forschungszentrum (DRFZ)
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-12820
• DOI: 10.1073/pnas.2310864121
• 发表日期: 2024-05-28
• 关键词: host-defense; mice reveal; il-22; cells; inflammation; asthma; differentiation; interleukin-22; RECOGNITION; homeostasis

摘要

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.