Intranasal administration of Acinetobacter lwoffii in a murine model of asthma induces IL‐6‐mediated protection associated with cecal microbiota changes

Medientyp: E-Artikel
Titel: Intranasal administration of Acinetobacter lwoffii in a murine model of asthma induces IL‐6‐mediated protection associated with cecal microbiota changes
Beteiligte: Alashkar Alhamwe, Bilal; Gao, Zhan; Alhamdan, Fahd; Harb, Hani; Pichene, Matthieu; Garnier, Abel; El Andari, Jihad; Kaufmann, Andreas; Graumann, Peter L.; Kesper, Dörthe; Daviaud, Christian; Garn, Holger; Tost, Jörg; Potaczek, Daniel P.; Blaser, Martin J.; Renz, Harald
Erschienen: Wiley, 2023
Erschienen in: Allergy
Sprache: Englisch
DOI: 10.1111/all.15606
ISSN: 0105-4538; 1398-9995
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Beschreibung: <jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Early‐life exposure to certain environmental bacteria including <jats:italic>Acinetobacter lwoffii</jats:italic> (<jats:italic>AL</jats:italic>) has been implicated in protection from chronic inflammatory diseases including asthma later in life. However, the underlying mechanisms at the immune‐microbe interface remain largely unknown.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>The effects of repeated intranasal <jats:italic>AL</jats:italic> exposure on local and systemic innate immune responses were investigated in wild‐type and <jats:italic>Il6</jats:italic><jats:sup><jats:italic>−/−</jats:italic></jats:sup>, <jats:italic>Il10</jats:italic><jats:sup><jats:italic>−/−</jats:italic></jats:sup>, and <jats:italic>Il17</jats:italic><jats:sup><jats:italic>−/−</jats:italic></jats:sup> mice exposed to ovalbumin‐induced allergic airway inflammation. Those investigations were expanded by microbiome analyses. To assess for <jats:italic>AL</jats:italic>‐associated changes in gene expression, the picture arising from animal data was supplemented by in vitro experiments of macrophage and T‐cell responses, yielding expression and epigenetic data.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The asthma preventive effect of <jats:italic>AL</jats:italic> was confirmed in the lung. Repeated intranasal <jats:italic>AL</jats:italic> administration triggered a proinflammatory immune response particularly characterized by elevated levels of IL‐6, and consequently, IL‐6 induced IL‐10 production in CD4<jats:sup>+</jats:sup> T‐cells. Both IL‐6 and IL‐10, but not IL‐17, were required for asthma protection. <jats:italic>AL</jats:italic> had a profound impact on the gene regulatory landscape of CD4<jats:sup>+</jats:sup> T‐cells which could be largely recapitulated by recombinant IL‐6. <jats:italic>AL</jats:italic> administration also induced marked changes in the gastrointestinal microbiome but not in the lung microbiome. By comparing the effects on the microbiota according to mouse genotype and <jats:italic>AL</jats:italic>‐treatment status, we have identified microbial taxa that were associated with either disease protection or activity.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>These experiments provide a novel mechanism of <jats:italic>Acinetobacter lwoffii</jats:italic>‐induced asthma protection operating through IL‐6‐mediated epigenetic activation of IL‐10 production and with associated effects on the intestinal microbiome.</jats:p></jats:sec>

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