| First Author | Shaabani N | Year | 2021 |
| Journal | Cell Physiol Biochem | Volume | 55 |
| Issue | 3 | Pages | 256-264 |
| PubMed ID | 33984198 | Mgi Jnum | J:331905 |
| Mgi Id | MGI:7386986 | Doi | 10.33594/000000370 |
| Citation | Shaabani N, et al. (2021) IFN-beta, but not IFN-alpha, is Responsible for the Pro-Bacterial Effect of Type I Interferon. Cell Physiol Biochem 55(3):256-264 |
| abstractText | 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 those which suppress cytotoxic T cells to avoid immunopathology. During certain bacterial infections, IFN-I signaling exerts largely detrimental effects. Although the IFN-I family of proteins all share one common receptor, biologic responses to signaling vary depending on IFN-I subtype. Here, we asked if one IFN-I subtype dominates the pro-bacterial effect of IFN-I signaling and found that control of Listeria monocytogenes (L.m.) infection is more strongly suppressed by IFN-beta than IFN-alpha. METHODS: To study this, we measured bacterial titers in IFNAR(-/-), IFN-beta(/), Stat2(-/-), Usp18(fl/fl) and Usp18(fl/fl) x CD11c-Cre mice models in addition to IFN-I blocking antibodies. Moreover, we measured interferon stimulated genes in bone marrow derived dendritic cells after treatment with IFN-alpha4 and IFN-beta. RESULTS: Specifically, we show that genetic deletion of IFN-beta or antibody-mediated IFN-beta neutralization was sufficient to reduce bacterial titers to levels similar to those observed in mice that completely lack IFN-I signaling (IFNAR(-/-) mice). However, IFN-alpha blockade failed to significantly reduce L.m. titers, suggesting that IFN-beta is the dominant IFN-I subtype responsible for the pro-bacterial effect of IFN-I. Mechanistically, when focusing on IFN-I signals to dendritic cells, we found that IFN-beta induces ISGs more robustly than IFN-alpha, including USP18, the protein we previously identified as driving the pro-bacterial effects of IFN-I. Further, we found that this induction was STAT1/STAT2 heterodimer- or STAT2/STAT2 homodimer-dependent, as STAT2-deficient mice were more resistant to L.m. infection. CONCLUSION: In conclusion, IFN-Beta is the principal member of the IFN-I family responsible for driving the pro-bacterial effect of IFN-I. |
