Commensal bacteria promote type I interferon signaling to maintain immune tolerance in mice

• DOI: 10.1084/jem.20230063
• Publication Date: 2023-12-12T14:36:31Z
• Authors: Adriana Vasquez A...; Chia-Yun Hsu; Renee E. Oles; Kazuhiko Matsuo; Luke R. Loomis; Ekaterina Buzun; Marvic Carrillo T...; Romana R. Gerner; Hsueh-Han Lu; Sohee Kim; Ziyue Zhang; Jong Hwee Park; Paul Rivaud; Matt Thomson; Li-Fan Lu; Booki Min; Hiutung Chu
• Keywords: Bacteroides fragilis

Type I interferons (IFNs) exert a broad range of biological effects important in coordinating immune responses, which have classically been studied the context pathogen clearance. Yet, whether immunomodulatory bacteria operate through IFN pathways to support intestinal tolerance remains elusive. Here, we reveal that commensal bacterium, Bacteroides fragilis, utilizes canonical antiviral modulate dendritic cells (DCs) and regulatory T cell (Treg) responses. Specifically, signaling is required for commensal-induced as IFNAR1-deficient DCs display blunted IL-10 IL-27 production response B. fragilis. We further establish IFN-driven critical shaping ensuing Foxp3+ Treg via IL-27Rα signaling. Consistent with these findings, single-cell RNA sequencing gut Tregs demonstrated colonization fragilis promotes distinct gene signature during inflammation. Altogether, our findings demonstrate role commensal-mediated tonic type