Die funktionelle Rolle der Typ-1 Interferon-induzierbaren Ubiquitin-spezifischen Peptidase 18 (USP18) während einer primären und sekundären bakteriellen Infektion.

• Antragsteller: Dr. Namir Shaabani
• Fachliche Zuordnung: Immunologie ; Biochemie
• Förderung: Förderung von 2018 bis 2021
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 397309475

• Erstellungsjahr: 2022

Zusammenfassung der Projektergebnisse

In summary, we define IFN-β-Usp18 axis as the main IFN-I signaling which promotes susceptibility to both primary and secondary bacterial infection through inhibiting anti-bacterial TNF-α signaling. Deletion of USP18 augments IFN-I signaling (8, 9) and is associated with prolonged JAK-STAT signaling which should increase rather than prevent L.m. infection. Targeting USP18 could be therapeutically applicable for treatment of bacterial infection without attenuating IFN-I signaling which could be important to controlling viral infections. In conclusion, targeting host USP18 will have the distinct advantage of exerting less selective pressure on bacterial populations and thereby attenuate the development of antibiotic resistance.

Projektbezogene Publikationen (Auswahl)

• The probacterial effect of type I interferon signaling requires its own negative regulator USP18. Sci Immunol. 2018 Sep 28;3(27). pii: eaau2125
  Shaabani N, Honke N, Nguyen N, Huang Z, Arimoto KI, Lazar D, Loe TK, Lang KS, Prinz M, Knobeloch KP, Zhang DE, Teijaro JR
  
• IFN-β, but not IFN-α, is Responsible for the Pro-Bacterial Effect of Type I Interferon. Biochem. 2021 May 14;55(3):256-264
  Shaabani N, Vartabedian VF, Nguyen N, Honke N, Huang Z, Teijaro JR