IFN-β, but not IFN-α, is Responsible for the Pro-Bacterial Effect of Type I Interferon

• DOI: 10.33594/000000370
• Publication Date: 2021-05-13T15:59:08Z
• Authors: Namir Shaabani; Vincent F. Vartab...; Nhan Nguyen; Nadine Honke; Zhe Huang; John R. Teijaro
• Keywords: Interferon type I; CD11c

BACKGROUND/AIMS: During an immune response, type I interferon (IFN-I) signaling induces a wide range of changes, including those which are required to overcome viral infection and suppress cytotoxic T cells avoid immunopathology. certain bacterial infections, IFN-I exerts largely detrimental effects. Although the family proteins all share one common receptor, biologic responses vary depending on subtype. Here, we asked if subtype dominates pro-bacterial effect found that control Listeria monocytogenes (L.m.) is more strongly suppressed by IFN-β than IFN-α. METHODS: To study this, measured titers in IFNAR-/-, IFN-β‑/‑, Stat2-/-, Usp18fl/fl x CD11c-Cre mice models addition blocking antibodies. Moreover, stimulated genes bone marrow derived dendritic after treatment with IFN-α4 IFN-β. RESULTS: Specifically, show genetic deletion or antibody-mediated neutralization was sufficient reduce levels similar observed completely lack (IFNAR-/- mice). However, IFN-α blockade failed significantly L.m. titers, suggesting dominant responsible for IFN-I. Mechanistically, when focusing signals cells, ISGs robustly IFN-α, USP18, protein previously identified as driving effects Further, this induction STAT1/STAT2 heterodimer- STAT2/STAT2 homodimer-dependent, STAT2-deficient were resistant infection. CONCLUSION: In conclusion, IFN-Β principal member