Salmonella SopB suppresses post-transcriptionally regulated cytokine release to reduce early tissue inflammation and delay disease progression
- Nour Diab
- Chiun Huei Yong
- Eva-Lena Stange
- Marlène S. Birk
- Matthias A. Schmitz
- Stefan Düsterhöft
- Jonas Pes
- Kira Noemi Ferle
- Isabel Karkossa
- Kristin Schubert
- Jörg Deiwick
- Mihael Vucur
- Tom Luedde
- Natalia Torow
- Andreas Ludwig
- Aline Dupont
- Joel Selkrig
- Martin von Bergen
- Michael Hensel
- Kaiyi Zhang
- Mathias W. Hornef
2026-07-06
Salmonella enterica subsp. enterica serovar Typhimurium ( S . Typhimurium) manipulates cellular processes through the translocation of effector molecules into the host cell cytosol. Using a recently established neonatal S . Typhimurium infection model, we provide functional insights into how Salmonella outer protein B (SopB) suppresses early mucosal tissue inflammation and prolongs host survival. Mechanistically, SopB prevents a disintegrin and metalloprotease 17 (ADAM17) activation, plasma membrane translocation and the release of membrane-bound TNFα from enterocytes and reduces epithelial secretion of IL-18 via mTOR-controlled secretory autophagy. This abolishes the early epithelial transcriptional response and reduces immune cell recruitment and programmed cell death-mediated mucosal barrier disruption delaying disease progression. The immunosuppressive effect of SopB is independent of the C-terminally encoded phosphatidylinositol phosphatase and phosphotransferase activity but requires an intact N-terminal domain. Also, it is restricted to the neonatal mouse model characterised by Salmonella pathogenicity island (SPI)1 type 3 secretion system (T3SS)-dependent enterocyte invasion-driven mucosal translocation. Thus, here we demonstrate that SopB suppresses the early, post-transcriptional regulation of epithelial cytokine release in an inositol phosphatase-independent manner likely promoting pathogen transmission.