The functional role of the type 1 interferon-inducible Ubiquitin Specific Peptidase 18 (USP18) during primary and secondary bacterial infection.

• Applicant: Dr. Namir Shaabani
• Subject Area: Immunology ; Biochemistry
• Term: from 2018 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 397309475

• Final Report Year: 2022

Final Report Abstract

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.

Publications

• 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
  (See online at https://doi.org/10.1126/sciimmunol.aau2125)
• 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
  (See online at https://doi.org/10.33594/000000370)