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

2023/11/16 by Adriana Vasquez Ayala, Chia-Yun Hsu, Renee Oles +14 · 1 voice · 2 citations
Biochemistry, Genetics and Molecular Biology · Immunology and Microbiology · #Gut microbiota and health #Immune Cell Function and Interaction #Immune Response and Inflammation

paper · pdf · doi:10.1084/jem.20230063

openalex publication_date 2023/11/16 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/31

Abstract

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

Citations

• Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota
• IL-17 and Th17 Cells
• Integrated analysis of multimodal single-cell data
• PANTHER: Making genome‐scale phylogenetics accessible to all

Cited by

• Clinical translation of microbiome research
• Immune-microbiome coordination defines interferon setpoints in healthy humans

Discussions

• Exciting news! Our lab’s first paper is published in JEM 🎉 Led by Adriana Vasquez Ayala, we show that commensal bacteria, such as Bacteroides fragilis, employ type IFN pathways to promote immune tole [bsky, 19 points, 1 comments]

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