2025/03/19 by Umesh Chopra, M C Sabu, Raju S Rajmani +3 · 1 voice
Medicine · Biochemistry, Genetics and Molecular Biology · Immunology and Microbiology · #Amoebic Infections and Treatments #Cancer Research and Treatments #Immune responses and vaccinations
paper · doi:10.1093/infdis/jiaf131
openalex publication_date 2025/03/19 · openalex created_date 2025/03/19 · openalex updated_date 2026/07/28
The upregulation of programmed death ligand 1 (PD-L1) by various pathogens is a recognized strategy to evade the adaptive immune response. Salmonella infection also upregulates PD-L1 levels; however, the underlying mechanism remains unclear. Our study reveals that this upregulation is mediated by Salmonella pathogenicity island 2 (SPI-2) effectors, as paraformaldehyde fixed and STMΔssaV fail to alter PD-L1 levels. We have further investigated the role of the SPI-2 effector SseL (a deubiquitinase) in PD-L1 upregulation, and our study reveals SseL to be crucial for upregulating PD-L1 in vitro as well as in vivo murine models. STMΔsseL exhibits colonization defects in secondary infection sites such as the liver and spleen. Notably, STMΔsseL infected mice show earlier mortality associated with heightened inflammation. Mechanistically, SseL stabilizes β-catenin, which translocates to the nucleus and leads to PD-L1 transcription, which is abrogated by the β-catenin/TCF inhibitor FH535. Collectively, our study elucidates the mechanism by which Salmonella mediates immune suppression through PD-L1 upregulation.